Compounds modulating C-kit activity

ABSTRACT

Compounds with 7-azaindole core structure with activity toward the receptor protein tyrosine kinase c-kit, compositions useful for treatment c-kit-mediate diseases or conditions, and methods of use thereof, are provided. Further provided are methods of c-kit ligand identification and design.

CROSS REFERENCE TO RELATED PATENT APPLICATIONS

This application is a divisional of Ibrahim et al., U.S. Non-Provisionalapplication Ser. No. 11/154,988, filed Jun. 16, 2005, which claims thebenefit of Ibrahim et al. U.S. Prov. App. No. 60/580,898, filed Jun. 17,2004, and Ibrahim et al. U.S. Prov. App. No. 60/682,076, filed May 17,2005, each of which are incorporated herein by reference in theirentireties including all specifications, figures, and tables, and forall purposes.

FIELD OF THE INVENTION

This invention relates to the development of ligands for c-kit and usesof such ligands.

BACKGROUND OF THE INVENTION

The information provided is intended solely to assist the understandingof the reader. None of the information provided nor references cited isadmitted to be prior art to the present invention. Each of thereferences cited is incorporated herein in its entirety.

Receptor protein tyrosine kinases (RPTKs) regulate key signaltransduction cascades that control cellular growth and proliferation.The Stem Cell Factor (SCF) receptor c-kit is a type III transmembraneRPTK that includes five extracellular immunoglobulin (IG) domains, asingle transmembrane domain, and a split cytoplasmic kinase domainseparated by a kinase insert segment. C-kit plays an important role inthe development of melanocytes, mast, germ, and hematopoietic cells.

Stem Cell Factor (SCF) is a protein encoded by the SI locus, and hasalso been called kit ligand (KL) and mast cell growth factor (MGF),based on the biological properties used to identify it (reviewed inTsujimura, Pathol Int 1996, 46:933-938; Loveland, et al., J. Endocrinol1997, 153:337-344; Vliagoftis, et al., Clin Immunol 1997, 100:435-440;Broudy, Blood 1997, 90:1345-1364; Pignon, Hermatol Cell Ther 1997,39:114-116; and Lyman, et al., Blood 1998, 91:1101-1134.). Herein we usethe abbreviation SCF to refer to the ligand for the c-Kit RTK.

SCF is synthesized as a transmembrane protein with a molecular weight of220 or 248 Dalton, depending on alternative splicing of the mRNA toencode exon 6. The larger protein can be proteolytically cleaved to forma soluble, glycosylated protein which noncovalently dimerizes. Both thesoluble and membrane-bound forms of SCF can bind to and activate c-Kit.For example, in the skin, SCF is predominantly expressed by fibroblasts,keratinocytes, and endothelial cells, which modulate the activity ofmelanocytes and mast cells expressing c-Kit. In bone, marrow stromalcells express SCF and regulate hematopoiesis of c-Kit expressing stemcells. In the gastrointestinal tract, intestinal epithelial cellsexpress SCF and affect the interstitial cells of Cajal andintraepithelial lymphocytes. In the testis, sertoli cells and granulosacells express SCF which regulates spermatogenesis by interaction withc-Kit on germ cells.

Additional RPTK proteins, for example Ret, and NTRK1, have beendescribed (Takahashi & Cooper, Mol Cell Biol. 1987, 7:1378-85; Bothwell,Cell. 1991, 65:915-8.). Ret and NTRK1 play a role in the development andmaturation of specific components of the nervous system. Alterations inRet and NTRK1 have been associated with several human diseases,including some forms of cancer and developmental abnormalities. Thecorrelation between genetic alteration and the appearance of variousdiseases has contributed to the concept that one gene can be responsiblefor more than one disease. Moreover, genetic alterations in both Ret andNTRK1 have been observed that belong to either “gain of function” or“loss of function” class of mutations. In fact, receptor rearrangementsor point mutations convert Ret and NTRK1 into dominantly actingtransforming genes leading to thyroid tumors, whereas inactivatingmutations, associated with Hirschsprung's disease (HSCR) and congenitalinsensitivity to pain with anhidrosis (CIPA), impair Ret and NTRK1functions, respectively.

A co-crystal structure of c-kit kinase domain with the compound STI-571(Gleevec, Imatinib) is reported by Mol et al. (J. Biol. Chem. 2003,278:31461-4). A structure of auto-inhibited c-kit, along with astructure of c-kit in complex with STI-571 is described by Mol et al.,(J. Biol Chem. 2004, 279:31655-63). Cloning, crystallization conditionsand structure determination are also described.

Modulation of c-Kit using indolinone compounds is described in Lipson etal., U.S. 20040002534 (U.S. application Ser. No. 10/600,868, filed Jun.23, 2003).

Aberrant expression and/or activation of c-Kit has been implicated in avariety of pathologic states. For example, evidence for a contributionof c-Kit to neoplastic pathology includes its association with leukemiasand mast cell tumors, small cell lung cancer, testicular cancer, andsome cancers of the gastrointestinal tract and central nervous system.In addition, c-Kit has been implicated in playing a role incarcinogenesis of the female genital tract sarcomas of neuroectodermalorigin, and Schwann cell neoplasia associated with neurofibromatosis. Itwas found that mast cells are involved in modifying the tumormicroenvironment and enhancing tumor growth (Yang et al., J Clin Invest.2003, 112:1851-1861; Viskochil, J Clin Invest. 2003, 112:1791-1793).Accordingly, there is a need in the art for modulators of c-kitactivity.

SUMMARY OF THE INVENTION

The present invention relates to compounds with activity toward c-Kit,and to methods of designing such compounds. In particular, the inventionprovides compounds of Formula I as described below. Thus, the inventionprovides compounds that can be used for therapeutic and/or prophylacticmethods involving modulation of c-Kit.

The compounds of Formula I have the following structure:

wherein:

-   -   R¹ and R⁵ are independently hydrogen, halo, hydroxy, substituted        oxy, thiol, substituted thiol, optionally substituted lower        alkyl, optionally substituted lower alkenyl, optionally        substituted lower alkynyl, optionally substituted cycloalkyl,        optionally substituted cycloalkylalkyl, optionally substituted        heterocyclyl, optionally substituted heterocyclylalkyl,        optionally substituted aryl, optionally substituted aralkyl,        optionally substituted heteroaryl, optionally substituted        heteroaralkyl, —C(X) NR¹⁶R¹⁷, —C(X)R²⁰, or —NR²²R²³;    -   R³ and R⁴ are independently hydrogen, halo, hydroxy, substituted        oxy, thiol, substituted thiol, optionally substituted lower        alkyl, optionally substituted lower alkenyl, optionally        substituted lower alkynyl, optionally substituted cycloalkyl,        optionally substituted cycloalkylalkyl, optionally substituted        heterocyclyl, optionally substituted heterocyclylalkyl,        optionally substituted aryl, optionally substituted aralkyl,        optionally substituted heteroaryl, or optionally substituted        heteroaralkyl, —C(X)R²⁰, —C(X)NR¹⁶R¹⁷, —S(O)₂NR¹⁶R¹⁷, —NR²²R²³,        or —S(O)_(n)R²¹;    -   R² is hydrogen, halo, hydroxy, substituted oxy, thiol,        substituted thiol, optionally substituted lower alkyl,        optionally substituted lower alkenyl, optionally substituted        lower alkynyl, optionally substituted cycloalkyl, optionally        substituted cycloalkylalkyl, optionally substituted        heterocyclyl, optionally substituted heterocyclylalkyl,        optionally substituted aryl, optionally substituted aralkyl,        optionally substituted heteroaryl, or optionally substituted        heteroaralkyl, —C(X)R²⁰, —C(X)NR¹⁶R¹⁷, —S(O)₂NR¹⁶R¹⁷, —NR²²R²³,        —S(O)_(n)R²¹, or —X¹—X²—X³—X⁴    -   wherein:        -   X¹ is selected from the group consisting of lower alkylene,            substituted lower alkylene, —C(O)—, —CH₂C(O)—, —C(O)CH₂—,            —C(S)—, —CH₂C(S)—, —C(S)CH₂—, —O—, —S—, —S(O₂)—, and            —NR^(a)—,            -   wherein:                -   R¹ is selected from the group consisting of                    hydrogen, lower alkyl and lower alkyl substituted                    with fluoro, hydroxyl, alkoxy, thiol, thioalkoxy, or                    amino, provided, however, that hydroxyl, alkoxy,                    thiol, thioalkyoxy or amino are not substituted at                    the carbon bound to the nitrogen of —NR^(a)—;        -   X² is selected from the group consisting of arylene and            heteroarylene;        -   X³ is selected from the group consisting of

-   -   -   -   wherein:                -   R^(b) at each occurrence is independently selected                    from the group consisting of hydrogen, lower alkyl                    and lower alkyl substituted with fluoro, hydroxyl,                    alkoxy, thiol, thioalkoxy, or amino, provided,                    however, that hydroxyl, alkoxy, thiol, thioalkyoxy                    or amino are not substituted at the carbon bound to                    the nitrogen of NR^(b); and                -   R^(e) is selected from the group consisting of                    alkylene and substituted alkylene; and

        -   X⁴ is selected from the group consisting of alkyl,            substituted alkyl, and

-   -   -   -   wherein                -   C² is selected from the group consisting of aryl and                    heteroaryl;                -   R^(d) is selected from the group consisting of                    halogen, lower alkyl, substituted lower alkyl,                    optionally substituted lower alkoxy, optionally                    substituted alkylthio, optionally substituted                    alkenyl, optionally substituted alkynyl, optionally                    substituted amine, optionally substituted amido,                    carboxyl, hydroxyl, optionally substituted aryl,                    aryloxy, optionally substituted heterocycle,                    optionally substituted heteroaryl, nitro, cyano,                    thiol, and sulfonylamino; and                -   m is in the range 0-2;

    -   R¹⁶ and R¹⁷ are independently hydrogen, optionally substituted        lower alkyl, optionally substituted lower alkenyl, provided,        however, that nitrogen is not attached to the alpha carbon of        the alkene bond; optionally substituted lower alkynyl, provided,        however, that nitrogen is not attached to the alpha carbon of        the alkyne bond; optionally substituted cycloalkyl, optionally        substituted cycloalkylalkyl, optionally substituted        heterocyclyl, optionally substituted heterocyclylalkyl,        optionally substituted aryl, optionally substituted aralkyl,        optionally substituted heteroaryl, optionally substituted        heteroaralkyl; or

-   R¹⁶ and R¹⁷ together with the nitrogen form an optionally    substituted 5-7 membered heterocyclic or heteroaryl ring;

-   R²⁰ is hydroxyl, substituted oxy, optionally substituted amine,    optionally substituted lower alkyl, optionally substituted lower    alkenyl, provided, however, that C(X)— is not attached to the alpha    carbon of the alkene bond, optionally substituted lower alkynyl,    provided, however, that —C(X)— is not attached to the alpha carbon    of the alkyne bond, optionally substituted cycloalkyl, optionally    substituted cycloalkylalkyl, optionally substituted heterocyclyl,    optionally substituted heterocyclylalkyl, optionally substituted    aryl, optionally substituted aralkyl, optionally substituted    heteroaryl, or optionally substituted heteroaralkyl;

-   R²¹ is hydrogen provided n=0, optionally substituted lower alkyl,    optionally substituted amine, optionally substituted lower alkenyl,    provided, however, that —S(O)_(n)— is not attached to the alpha    carbon of the alkene bond, optionally substituted lower alkynyl,    provided, however, that —S(O)_(n)— is not attached to the alpha    carbon of the alkyne bond, optionally substituted cycloalkyl,    optionally substituted cycloalkylalkyl, optionally substituted    heterocyclyl, optionally substituted heterocyclylalkyl, optionally    substituted aryl, optionally substituted aralkyl, optionally    substituted heteroaryl, optionally substituted heteroaralkyl;

-   R²² and R²³ are independently hydrogen, optionally substituted lower    alkyl, optionally substituted lower alkenyl, provided, however, that    nitrogen is not attached to the alpha carbon of the alkene bond,    optionally substituted lower alkynyl, provided, however, that    nitrogen is not attached to the alpha carbon of the alkyne bond,    optionally substituted cycloalkyl, optionally substituted    cycloalkylalkyl, optionally substituted heterocyclyl, optionally    substituted heterocyclylalkyl, optionally substituted aryl,    optionally substituted aralkyl, optionally substituted heteroaryl,    optionally substituted heteroaralkyl, —C(X)R²⁰, —C(X)NR¹⁶R¹⁷, and    —S(O)₂R²¹; or

-   R²² and R²³ together with the nitrogen form an optionally    substituted 5-7 membered heterocyclic or heteroaryl ring;

-   X is O or S; and

-   n is 0, 1, or 2.

For the compounds described herein, the following definitions apply:

“Halo” and “halogen” refer to all halogens including chloro (Cl), fluoro(F), bromo (Br), or iodo (I).

“Hydroxyl” and “hydroxy” refer to the group —OH.

“Substituted oxy” refers to the group —OR^(f), where R^(f) is alkyl,substituted alkyl, acyl, substituted acyl, aryl, substituted aryl,heteroaryl, substituted heteroaryl, aralkyl, substituted aralkyl,heterocyclylalkyl, substituted heterocyclylalkyl, heteroarylalkyl,substituted heteroarylalkyl, cycloalkyl, substituted cycloalkyl,heterocyclyl, or substituted heterocyclyl.

“Thiol” and “mercapto” refer to the group —SH.

“Substituted thiol” refers to the group —SR, where R is alkyl,substituted alkyl, acyl, substituted acyl, aryl, substituted aryl,heteroaryl, substituted heteroaryl, aralkyl, substituted aralkyl,heterocyclylalkyl, substituted heterocyclylalkyl, heteroarylalkyl,substituted heteroarylalkyl, cycloalkyl, substituted cycloalkyl,heterocyclyl, or substituted heterocyclyl.

“Alkyl” refers to an alkane-derived radical containing from 1 to 20,preferably 1 to 15, carbon atoms. Alkyl includes straight chain alkyl,branched alkyl and cycloalkyl. Straight chain or branched alkyl groupscontain from 1-15, preferably 1 to 8, more preferably 1-6, yet morepreferably 1-4 and most preferably 1-2, carbon atoms, such as methyl,ethyl, propyl, isopropyl, butyl, t-butyl, and the like. Alkyl alsoincludes straight chain or branched alkyl groups that contain or areinterrupted by one or more cycloalkyl portions. Examples of thisinclude, but are not limited to, 4-(isopropyl)-cyclohexylethyl or2-methyl-cyclopropylpentyl. The alkyl group is attached at any availablepoint to produce a stable compound.

A “substituted alkyl” is an alkyl group independently substituted with 1or more, e.g., 1, 2, or 3, groups or substituents such as halo, hydroxy,optionally substituted alkoxy, optionally substituted alkylthio,alkylsulfinyl, alkylsulfonyl, acyloxy, optionally substituted aryl,optionally substituted aryloxy, optionally substituted heteroaryloxy,optionally substituted amino, optionally substituted amido, amidino,urea optionally substituted with alkyl, aryl, heteroaryl or heterocyclylgroups, aminosulfonyl optionally N-mono- or N,N-di-substituted withalkyl, aryl or heteroaryl groups, alkylsulfonylamino, arylsulfonylamino,heteroarylsulfonylamino, alkylcarbonylamino, arylcarbonylamino,heteroarylcarbonylamino, carboxyl, heterocycle, substituted heterocycle,heteroaryl, substituted heteroaryl, nitrogen, cyano, thiol,sulfonylamino, or the like attached at any available point to produce astable compound.

“Lower alkyl” refers to an alkyl group having 1-6 carbon atoms.

A “substituted lower alkyl” is a lower alkyl which is substituted with 1or more, e.g., 1, 2, or 3, groups or substitutents as defined in [0020]attached at any available point to produce a stable compound.

“Cycloalkyl” refers to saturated or unsaturated, non-aromaticmonocyclic, bicyclic or tricyclic carbon ring system of 3-8, morepreferably 3-6, ring members per ring, such as cyclopropyl, cyclopentyl,cyclohexyl, adamantyl, and the like.

A “substituted cycloalkyl” is a cycloalkyl which is independentlysubstituted with 1 or more, e.g., 1, 2, or 3, groups or substitutents asdefined in [0020], optionally substituted alkyl, optionally substitutedalkenyl, or optionally substituted alkynyl, attached at any availablepoint to produce a stable compound.

“Alkylene” refers to a divalent alkane-derived radical containing 1-20,preferably 1-15, carbon atoms, straight chain or branched, from whichtwo hydrogen atoms are taken from the same carbon atom or from differentcarbon atoms. Examples of alkylene include, but are not limited to,methylene —CH₂—, ethylene —CH₂CH₂—, and the like.

A “substituted alkylene” is an alkylene which is independentlysubstituted with 1 or more, e.g., 1, 2, or 3, groups or substitutents asdefined in [0020] attached at any available point to produce a stablecompound.

A “lower alkylene” is an alkylene containing 1-6 carbon atoms.

A “substituted lower alkylene” is a lower alkylene which isindependently substituted with 1 or more, e.g., 1, 2, or 3, groups orsubstitutents as defined in [0020] attached at any available point toproduce a stable compound.

“Alkenyl” refers to a straight chain, branched, or cyclic hydrocarboncontaining 2-20, preferably 2-17, more preferably 2-10, even morepreferably 2-8, most preferably 2-4, carbon atoms, and which contains atleast one, preferably 1-3, more preferably 1-2, and most preferably one,carbon to carbon double bond. In the case of a cycloalkyl group,conjugation of more than one carbon to carbon double bond is not such asto confer aromaticity to the ring. Carbon to carbon double bonds may beeither contained within a cycloalkyl portion, with the exception ofcyclopropyl, or within a straight chain or branched portion. Examples ofalkenyl groups include, but are not limited to, ethenyl, propenyl,isopropenyl, butenyl, cyclohexenyl, cyclohexenylalkyl, and the like.

A “substituted alkenyl” is an alkenyl which is independently substitutedwith 1 or more, e.g., 1, 2, or 3, groups or substituents as defined in[0020], attached at any available point to produce a stable compound.

“Lower alkenyl” refers to an alkenyl group having 1-6 carbon atoms.

A “substituted lower alkenyl” is a lower alkenyl which is substitutedwith 1 or more, e.g., 1, 2, or 3, groups or substitutents as defined in[0020] attached at any available point to produce a stable compound.

“Alkynyl” refers to a straight chain or branched hydrocarbon containing2-20, preferably 2-17, more preferably 2-10, even more preferably 2-8,most preferably 2-4, carbon atoms, and which contains at least one,preferably one, carbon to carbon triple bond. Examples of alkynyl groupsinclude, but are not limited to, ethynyl, propynyl, butynyl, and thelike.

A “substituted alkynyl” is an alkynyl which is independently substitutedwith 1 or more, e.g., 1, 2, or 3, groups or substituents as defined in[0020], attached at any available point to produce a stable compound.

“Lower alkynyl” refers to an alkynyl group having 1-6 carbon atoms.

A “substituted lower alkynyl” is a lower alkynyl which is substitutedwith 1 or more, e.g., 1, 2, or 3, groups or substitutents as defined in[0020] attached at any available point to produce a stable compound.

“Alkoxy” denotes the group —OR^(e), where R^(f) is lower alkyl.

“Substituted alkoxy” denotes the group —OR^(f′), where R^(f′) issubstituted lower alkyl.

“Alkylthio” or “thioalkoxy” refers to the group —S—R, where R is loweralkyl,

“Substituted alkylthio” or “substituted thioalkoxy” refers to the group—S—R, where R is substituted lower alkyl.

“Sulfinyl” denotes the group —S(O)—.

“Substituted sulfinyl” denotes the group —S(O)—R, where R is loweralkyl, substituted lower alkyl, aryl, substituted aryl, heteroaryl,substituted heteroaryl, heteroaralkyl, substituted heteroaralkyl,aralkyl or substituted aralkyl.

“Sulfonyl” denotes the group —S(O)₂—.

“Substituted sulfonyl” denotes the group —S(O)₂—R, where R is loweralkyl, substituted lower alkyl, aryl, substituted aryl, heteroaryl,substituted heteroaryl, heteroaralkyl, substituted heteroaralkyl,aralkyl or substituted aralkyl.

“Sulfonylamino” denotes the group —NRS(O)₂—, where R is hydrogen orlower alkyl.

“Substituted sulfonylamino” denotes the group —NR^(a)S(O)₂—R^(b), whereR^(a) is hydrogen or lower alkyl and R^(b) is lower alkyl, substitutedlower alkyl, cycloalkyl, substituted cycloalkyl, heterocyclyl,substituted heterocyclyl, aryl, substituted aryl, heteroaryl,substituted heteroaryl, heteroarallyl, substituted heteroaralkyl,aralkyl or substituted aralkyl.

“Acyl” denotes the group —C(O)R^(h), where R^(h) is hydrogen, loweralkyl, aryl, heteroaryl and the like.

“Substituted acyl” denotes the group —C(O)R^(h′), where R^(h′) issubstituted lower alkyl, substituted aryl, substituted heteroaryl andthe like.

“Acyloxy” denotes the group —OC(O)R^(h), where R^(h) is hydrogen, loweralkyl, substituted lower alkyl, aryl, substituted aryl, heteroaryl,substituted heteroaryl and the like.

“Aryloxy” denotes the group —OAr, where Ar is an aryl or substitutedaryl group.

“Heteroaryloxy” denotes groups —OHet, wherein Het is an optionallysubstituted heteroaryl group.

“Amino” or “amine” denotes the group —NH₂.

“Substituted amino” or “substituted amine” denotes the group—NR^(i)R^(j), wherein R^(i) and R^(j) are independently hydrogen, loweralkyl, substituted lower alkyl, aryl, substituted aryl, heteroaryl,substituted heteroaryl, acyl, substituted acyl, sulfonyl or substitutedsulfonyl, provided, however, that at least one of R^(i) and R^(j) is nothydrogen. R^(i)R^(j) in combination with the nitrogen may form anoptionally substituted heterocyclic or heteroaryl ring.

“Amido” denotes the group —C(O)NH₂

“Substituted amido” denotes the group —C(O)NR^(k)R^(l), wherein R^(k)and R^(l) are independently hydrogen, lower alkyl, substituted loweralkyl, aryl, substituted aryl, heteroaryl, or substituted heteroaryl,provided, however, that at least one of R^(k) and R^(l) is not hydrogen.R^(k)R^(l) in combination with the nitrogen may form an optionallysubstituted heterocyclic or heteroaryl ring.

“Amidino” denotes the group —C(═NR^(m))NR^(n)R^(o), wherein R^(m),R^(n), and R^(o) are independently hydrogen or optionally substitutedlower alkyl.

“Alkylsulfinyl” denotes the group —S(O)R^(p), wherein R^(p) isoptionally substituted alkyl.

“Alkylsulfonyl” denotes the group —S(O)₂R^(p), wherein R^(p) isoptionally substituted alkyl.

“Alkylsulfonylamino” denotes the group —NR^(q)S(O)₂R^(p), wherein R^(p)is optionally substituted alkyl, and R^(q) is hydrogen or lower alkyl.

“Arylsulfonylamino” denotes the group —NR^(q)S(O)₂R^(s), wherein R^(s)is optionally substituted aryl, and R^(q) is hydrogen or lower alkyl.

“Heteroarylsulfonylamino” denotes the group —NR^(q)S(O)₂R^(t), whereinR^(t) is optionally substituted heteroaryl, and R^(q) is hydrogen orlower alkyl.

“Carbonylamino” denotes the group —NR^(q)C(O)H, wherein R^(q) ishydrogen or lower alkyl.

“Substituted carbonylamino” denotes the group —NR^(q)C(O)R^(p), whereinR^(q) is hydrogen or lower alkyl and R^(p) is optionally substitutedalkyl, optionally substituted cycloalkyl, optionally substitutedheterocyclyl, optionally substituted aryl, or optionally substitutedheteroaryl.

“Alkylcarbonylamino” denotes the group —NR^(q)C(O)R^(p), wherein R^(p)is optionally substituted alkyl, and R^(q) is hydrogen or lower alkyl.

“Arylcarbonylamino” denotes the group —NR^(q)C(O)R^(s), wherein R^(s) isoptionally substituted aryl, and R^(q) is hydrogen or lower alkyl.

“Heteroarylcarbonylamino” denotes the group —NR^(q)C(O) R^(t), whereinR^(t) is optionally substituted aryl, and R^(q) is hydrogen or loweralkyl.

“Carboxyl” denotes the group —C(O)OR^(r), wherein R^(r) is hydrogen,lower alkyl, substituted lower alkyl, aryl, substituted aryl,heteroaryl, or substituted heteroaryl.

“Aryl” means phenyl or naphthyl optionally fused with a cycloalkyl ofpreferably 5-7, more preferably 5-6, ring members.

“Arylene” means a divalent aryl

A “substituted aryl” is an aryl group which is independently substitutedwith 1 or more, e.g., 1, 2, or 3, groups or substituents as defined in[0020], optionally substituted alkyl, optionally substituted alkenyl, oroptionally substituted alkynyl, attached at any available point toproduce a stable compound.

“Heterocycle” or “heterocyclyl” means a saturated or unsaturated,non-aromatic carbocyclic group having a single ring or multiplecondensed rings, e.g. a cycloalkyl group having from 5 to 10 atoms inwhich from 1 to 3 carbon atoms in a ring are replaced by heteroatoms,such as O, S, N, and are optionally fused with benzo or heteroaryl of5-6 ring members and/or are optionally substituted. Heterocyclyl isintended to include oxidized S or N, such as sulfinyl, sulfonyl andN-oxide of a tertiary ring nitrogen. The point of attachment is at acarbon or nitrogen atom. Examples of heterocycle or heterocyclyl groupsare morpholino, tetrahydrofuranyl, dihydropyridinyl, piperidinyl,pyrrolidinyl, piperazinyl, dihydrobenzofuryl, dihydroindolyl, and thelike.

A “substituted heterocycle” or “substituted heterocyclyl” is aheterocycle substituted with 1 or more, e.g., 1, 2, or 3, substituentsas defined in [0020], optionally substituted alkyl, optionallysubstituted alkenyl, optionally substituted alkynyl, or oxo group,attached at any available point to produce a stable compound.

“Oxo” refers to an oxygen substituent double bonded to the attachedcarbon.

“Heteroaryl” means a monocyclic aromatic ring structure containing 5 or6 ring atoms, or a bicyclic aromatic group having 8 to 10 atoms,containing one or more, preferably 1-4, more preferably 1-3, even morepreferably 1-2, heteroatoms independently selected from the groupconsisting of O, S, and N. Heteroaryl is also intended to includeoxidized S or N, such as sulfinyl, sulfonyl and N-oxide of a tertiaryring nitrogen. A carbon or nitrogen atom is the point of attachment ofthe heteroaryl ring structure such that a stable aromatic ring isretained. Examples of heteroaryl groups are naphthpyridyl, pyridinyl,pyridazinyl, pyrazinyl, quinoxalyl, indolizinyl, benzo[b]thienyl,quinazolinyl, purinyl, indolyl, quinolinyl, pyrimidinyl, pyrrolyl,oxazolyl, thiazolyl, thienyl, isoxazolyl, oxathiadiazolyl, isothiazolyl,tetrazolyl, imidazolyl, triazinyl, furanyl, benzofuryl, indolyl, and thelike.

“Heteroarylene” means a divalent heteroaryl.

A “substituted heteroaryl” is a heteroaryl which is independentlysubstituted with 1 or more, e.g., 1, 2, or 3, groups or substituents asdefined in [0020], optionally substituted alkyl, optionally substitutedalkenyl, or optionally substituted alkynyl, attached at any availablepoint to produce a stable compound.

“Aralkyl” refers to the group —R—Ar where Ar is an aryl group and R islower alkylene.

“Substituted aralkyl” refers to the aralkyl group which is independentlysubstituted with 1 or more, e.g., 1, 2, or 3, groups or substituents asdefined in [0020], optionally substituted alkyl, optionally substitutedalkenyl, or optionally substituted alkynyl, attached at any availablepoint to produce a stable compound.

“Heterocyclylalkyl” refers to the group —R-Het where Het is aheterocycle group and R is a lower alkylene group.

“Substituted heterocyclylalkyl” refers to a heterocyclylalkyl groupwhich is independently substituted with 1 or more, e.g., 1, 2, or 3,groups or substituents as defined in [0020], optionally substitutedalkyl, optionally substituted alkenyl, optionally substituted alkynyl,or oxo group attached at any available point to produce a stablecompound.

“Cycloalkylalkyl” refers to the group —R-Cyc where Cyc is a cycloalkylgroup and R is a lower alkylene group.

“Substituted cycloalkylalkyl” refers to a cycloalkylalkyl group which isindependently substituted with 1 or more, e.g., 1, 2, or 3, groups orsubstituents as defined in [0020], optionally substituted alkyl,optionally substituted alkenyl, or optionally substituted alkynyl,attached at any available point to produce a stable compound.

“Heteroarylalkyl” and “heteroaralkyl” refer to the group —R-HetAr whereHetAr is an heteroaryl group and R lower alkylene.

“Substituted heteroarylalkyl” and “substituted heteroaralkyl” refer tothe heteroarylalkyl group which is independently substituted with 1 ormore, e.g., 1, 2, or 3, groups or substituents as defined in [0020],optionally substituted alkyl, optionally substituted alkenyl, oroptionally substituted alkynyl, attached at any available point toproduce a stable compound.

In reference to Formula I, the core structure shown above without thesubstituents is referred to as the “azaindole core.” For that azaindolecore, reference to ring atoms or ring positions is as shown in thefollowing structure:

In particular embodiments involving compounds of Formula I, R¹ and R⁵are hydrogen. In particular embodiments, compounds of Formula I haveother than hydrogen at R²; other than hydrogen at R³, other thanhydrogen at R⁴, other than hydrogen at R² and R³; and other thanhydrogen at R² and R⁴. In certain embodiments, the substitutions aslisted are the only substitutions; the substitutions as listed arecombined with R¹ and R⁵ as H; the substitutions as listed are combinedwith substitution at one other of the substitution positions shown inFormula I.

In one embodiment, the invention provides a method for treating asubject suffering from or at risk of a c-Kit mediated disease orcondition, comprising administering to the subject an effective amountof a compound of Formula I as given above.

In a further embodiment, the c-Kit mediated disease or condition whichis the object of treatment is associated with improperly regulatedkinase signal transduction.

In a further embodiment of the invention relating to the treatment of ac-Kit mediated disease or condition, the improperly regulated kinasesignal transduction is of mast cells.

In a further embodiment of the invention relating to the treatment of ac-Kit mediated disease or condition, the c-Kit mediated disease orcondition is mastocytosis, asthma, rheumatoid arthritis or chronicrhinitis.

In a further embodiment of the invention relating to the treatment of ac-Kit mediated disease or condition, the c-Kit mediated disease orcondition is a cell proliferative disorder, a fibrotic disorder, or ametabolic disorder.

In a further embodiment, the cell proliferative disorder is cancer.

In a further embodiment, the cancer is leukemia, mast cell tumor, smallcell lung cancer, testicular cancer, cancer of the gastrointestinaltract, cancer of the central nervous system, cancer of the femalegenital tract, sarcoma of neuroectodermal origin, or Schwann cellneoplasia associated with neurofibromatosis.

In a further embodiment of the invention relating to the treatment of ac-Kit mediated disease or condition, the c-Kit mediated disease orcondition is multiple sclerosis.

In particular embodiments, the compound of Formula I has a structureaccording to the following sub-generic structure, Formula Ia, where R²is as defined for Formula I. In another embodiment of Formula Ia, R² is—X¹—X²—X³—X⁴. where X¹, X², X³ and X⁴ are defined as in Formula I,

In another embodiment of the invention, with reference to Formula Ia,when —X¹—X²—X³—X⁴ is

then R^(d) is not F, Cl, CH₃ or CF₃.

In a further embodiment, X¹ is selected from the group consisting ofmethylene and substituted methylene.

In a further embodiment, X¹ is difluoromethylene or —C(O)—, furtherwherein X² is phenylene.

In a further embodiment, X² contains one or two nitrogen atoms.

In further embodiments, X² is pyridinediyl, pyrimidinediyl,pyrazinediyl, or pyridazinediyl.

In yet a further embodiment, X² is

In a further embodiment, X⁴ is

In further embodiments, X³ is

wherein:

R^(b) is hydrogen or lower alkyl; and

R^(c) is methylene or substituted methylene.

In further embodiments, X³ is —NHCH₂—, or —NHC(O)—, further wherein X²is heteroaryl.

In further embodiments, X³ is

and R^(b) is hydrogen or lower alkyl.

In a further embodiment, X⁴ is

wherein

-   R^(d) at each occurrence is independently halogen, lower alkyl,    substituted lower alkyl, optionally substituted lower alkoxy,    optionally substituted alkylthio, optionally substituted alkenyl,    optionally substituted alkynyl, optionally substituted amine,    optionally substituted amido, carboxyl, hydroxyl, optionally    substituted aryl, aryloxy, optionally substituted heterocycle,    heteroaryl, substituted heteroaryl, nitro, cyano, thiol, or    sulfonylamino; and-   m is in the range 0-2.

In a further embodiment, X⁴ is

and C² is thienyl, substituted thienyl, pyridinyl, pyrimidinyl,pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, or furanyl.

In a further embodiment, X⁴ is alkyl or substituted alkyl.

In a further embodiment, the invention provides a composition comprisinga pharmaceutically acceptable carrier and one or more compounds havingthe structure of Formula Ia

wherein:

-   R² is X¹—X²—X³—X⁴;-   X¹ is selected from the group consisting of lower alkylene,    substituted lower alkylene, —O—, —S—, and NR^(a),    -   wherein R^(a) is selected from the group consisting of hydrogen,        lower alkyl and lower alkyl substituted with fluoro, hydroxyl,        alkoxy, thiol, thioalkoxy, or amino, provided hydroxyl, alkoxy,        thiol, thioalkyoxy or amino are not substituted at the carbon        bound to the nitrogen of —NR^(a)—;-   X² is selected from the group consisting of arylene and    heteroarylene;-   X³ is selected from the group consisting of

-   -   wherein        -   R^(b) at each occurrence is independently selected from the            group consisting of hydrogen, lower alkyl, and lower alkyl            substituted with fluoro, hydroxyl, alkoxy, thiol,            thioalkoxy, or amino, provided hydroxyl, alkoxy, thiol,            thioalkyoxy or amino are not substituted at the carbon bound            to the nitrogen of NR^(b); and        -   R^(c) is selected from the group consisting of alkylene and            substituted alkylene; and

-   X⁴ is selected from the group consisting of alkyl, substituted    alkyl, and

-   -   wherein        -   C² is selected from the group consisting of aryl and            heteroaryl;        -   R^(d) is selected from the group consisting of halogen,            lower alkyl, substituted lower alkyl, optionally substituted            lower alkoxy, optionally substituted alkylthio, optionally            substituted alkenyl, optionally substituted alkynyl,            optionally substituted amine, optionally substituted amido,            carboxyl, hydroxyl, optionally substituted aryl, aryloxy,            optionally substituted heterocycle, optionally substituted            heteroaryl, nitro, cyano, thiol, and sulfonylamino; and    -   m is in the range 0-2;        provided, however, that the compound is not

provided, however, that the compound is not

pharmaceutically acceptable salts, prodrugs, and isomers thereof.

In a further embodiment, the invention provides a composition as givenabove, provided, however, that when X¹—X²—X³—X⁴ is

then R^(d) is not selected from the group consisting of F, Cl, CH₃, andCF₃.

In a further embodiment, the invention provides a method for treating asubject suffering from or at risk of a c-Kit mediated disease orcondition, wherein the method comprises administering to the subject aneffective amount of a composition of Formula I.

In a further aspect of the composition above, the c-Kit mediated diseaseor condition is associated with improperly regulated kinase signaltransduction.

In a further aspect of the composition above, the improperly regulatedkinase signal transduction is of mast cells.

In a further aspect of the composition above, the c-Kit mediated diseaseor condition is mastocytosis, asthma, or chronic rhinitis.

In a further aspect of the composition above, the c-Kit mediated diseaseor condition is a cell proliferative disorder, a fibrotic disorder, or ametabolic disorder.

In a further aspect of the composition above, the cell proliferativedisorder is cancer.

In a further aspect of the composition above, the cancer is leukemia,mast cell tumor, small cell lung cancer, testicular cancer, cancer ofthe gastrointestinal tract, cancer of the central nervous system, cancerof the female genital tract, sarcoma of neuroectodermal origin, orSchwann cell neoplasia associated with neurofibromatosis.

In a further aspect of the composition above, the c-Kit mediated diseaseor condition is multiple sclerosis.

Further to any of the above embodiments, when R¹, R³, R⁴ and R⁵ arehydrogen, R² is not

In reference to c-kit modulator compounds herein, specification of acompound or group of compounds includes pharmaceutically acceptablesalts of such compound(s) unless clearly indicated to the contrary,prodrugs, and all isomers.

Thus, in one aspect, the invention provides methods for treating ac-Kit-mediated disease or condition in an animal subject, e.g., a mammalsuch as a human, e.g., a disease or condition characterized by abnormalc-Kit activity (e.g., kinase activity), where the method involvesadministering to the subject a compound of Formula I.

As used herein, the term c-kit-mediated disease or condition refers to adisease or condition in which the biological function of c-Kit affectsthe development and/or course of the disease or condition, and/or inwhich modulation of c-Kit alters the development, course, and/orsymptoms.

Specific diseases or disorders which can be treated or prevented includethose described in the Detailed Description herein, and in thereferences cited therein. Exemplary diseases and conditions include butare not limited to cancer, asthma, arthritis, chronic rhinitis, multiplesclerosis, GIST, and mastocytosis disorders.

In a related aspect, compounds of Formula I can be used in thepreparation of a medicament for the treatment of a c-Kit-mediateddisease or condition, such as a cancer, asthma, arthritis, chronicrhinitis, multiple sclerosis, or other disease indicated herein.

In another aspect, the invention provides compounds of Formula I asdescribed herein (e.g., compounds that have advantageous levels ofactivity and/or selectivity on c-Kit). In certain embodiments, thecompounds are substituted at the 3-position of the core bicyclic ringstructure (azaindole core) with a substituent group that in orderincludes a first linker bound to a first aryl or heteroaryl group, whichis bound to a linker of 1 to 3 atoms bound to a second aryl orheteroaryl group. In certain embodiments including the just-described3-position substituent group, the first linker is methylene, ethylene,—C(O)—, —CH₂—C(O)—, —C(O)CH₂—, —C(S)—, —CH₂—C(S)—, —C(S)CH₂—, —O—, —S—,or —S(O₂)—; the first aryl or heteroaryl group is pyridinyl,pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl, triazolyl,thiazolyl, furanyl, or oxazolyl; the second linker is methyl amino—(NH—CH₂)—, ethyl amino —(NH—CH₂—CH₂)—, amide (—NH—C(O)—), sulfonamide(—NH—(SO₂)—) urea (—NH—C(O)—NH—), thiourea (—NH—C(S)—NH—), or sulfonylurea (—NH—S(O)₂—NH—); the second aryl or heteroaryl group is phenyl,pyridinyl, pyrimidinyl, pyrazinyl, pyridazinyl, pyrrolyl, imidazolyl,triazolyl, thiazolyl, furanyl, or oxazolyl; the second aryl orheteroaryl group is substituted with a lower alkyl group, a methylgroup, an ethyl group, a propyl group, a butyl group, a lower alkoxygroup, a methoxy group, an ethoxy group, a propoxy group, a butoxygroup, a halo substituted lower alkyl, —CH₂F, —CHF₂, —CF₃, halo, F, Cl.In further particular embodiments, the substitutent group at the3-position is each specific combination of the first linker, first arylor heteroaryl group, second linker, second aryl or heteroaryl group, andwith each of the specified substitutions on the second aryl orheteroaryl group. In particular embodiments, the second aryl orheteroaryl group is a 6-membered ring; the 6-membered ring issubstituted at the para position; the 6-membered ring is substituted atthe meta position; the 6-membered ring is substituted at the orthoposition; the 6-membered ring is substituted at the meta and parapositions. In particular embodiments, the second aryl or heteroarylgroup is a 5-membered ring; the 5-membered ring is substituted atposition adjacent to the atom bound to the second linker; the 5-memberedring is substituted at a position not adjacent to the atom bound to thesecond linker. In particular embodiments, the 3-position substitutentgroup is the only non-hydrogen substitutent on the azaindole core.

In particular embodiments, the compound has an IC₅₀ of less than 100 nM,less than 50 nM, less than 20 nM, less than 10 nM, less than 5 nM asdetermined in a generally accepted kinase activity assay. In certainembodiments, the selectivity of the compound is such that the compoundis at least 2-fold, 5-fold, 10-fold, or 100-fold more active withrespect to c-Kit than with respect to Ret. In certain embodiments, thecompound has in combination each pairing of activity (e.g., IC₅₀) andselectivity as specified in this paragraph

An additional aspect of this invention relates to compositions, thatinclude a therapeutically effective amount of a compound of Formula I(or a compound within a sub-group of compounds within any of the genericformulae) and at least one pharmaceutically acceptable carrier,excipient, and/or diluent. The composition can include a plurality ofdifferent pharmacologically active compounds, which can include aplurality of compounds of Formula I.

As used herein, the term “pharmaceutical composition” refers to aformulation suitable for administration to an intended animal subjectfor therapeutic purposes that contains at least one active compound andat least one pharmaceutically acceptable carrier or excipient.

The term “pharmaceutically acceptable” indicates that the indicatedmaterial does not have properties that would cause a reasonably prudentmedical practitioner to avoid administration of the material to apatient, taking into consideration the disease or conditions to betreated and the respective route of administration. For example, it iscommonly required that such a material be essentially sterile, e.g., forinjectibles.

In the present context, the terms “therapeutically effective” and“effective amount” indicates that the materials and amount of materialis effective to prevent, alleviate, or ameliorate one or more symptomsof a disease or medical condition, and/or to prolong the survival of thesubject being treated.

In a related aspect, the invention provides kits that include apharmaceutical composition as described herein. In particularembodiments, the pharmaceutical composition is packaged, e.g., in avial, bottle, flask, which may be further packaged, e.g., within a box,envelope, or bag; the pharmaceutical composition is approved by the U.S.Food and Drug Administration or similar regulatory agency foradministration to a mammal, e.g., a human; the pharmaceuticalcomposition is approved for administration to a mammal, e.g., a humanfor a c-Kit mediated disease or condition; the kit includes writteninstructions of use and/or other indication that the composition issuitable or approved for administration to a mammal, e.g., a human, fora c-Kit mediated disease or condition; the pharmaceutical composition ispackaged in unit does or single dose form, e.g., single dose pills,capsules, or the like.

In aspects of the present invention involving treatment or prophylaxisof a disease or conditions, the disease or condition is cancer, asthma,arthritis, chronic rhinitis, multiple sclerosis, a mastocytosisdisorder, or other disease.

The identification of compounds of Formula I with activity toward c-kitalso provides a method for identifying or developing additionalcompounds active on c-kit, e.g., improved modulators, by determiningwhether any of a plurality of test compounds of Formula I with activitytoward c-kit provides an improvement in one or more desiredpharmacologic properties relative to a reference compound with activitytoward c-kit, and selecting a compound 1f any, that has an improvementin the desired pharmacologic property, thereby providing an improvedmodulator.

In particular embodiments of modulator development, the desiredpharmacologic property is serum half-life longer than 2 hr or longerthan 4 hr or longer than 8 hr, aqueous solubility, oral bioavailabilitymore than 10%, oral bioavailability more than 20%.

Also in particular embodiments of modulator development, the process canbe repeated multiple times, i.e., multiple rounds of preparation ofderivatives and/or selection of additional related compounds andevaluation of such further derivatives of related compounds, e.g., 1, 2,3, 4, 5, 6, 7, 8, 9, 10 or more additional rounds.

In additional aspects, structural information about c-Kit is utilized,e.g., in conjunction with compounds of Formula I or a molecular scaffoldor scaffold core of Formula I.

The invention also provides a method for developing ligands binding toc-Kit, where the method includes identifying as molecular scaffolds oneor more compounds of Formula I that bind to a binding site of thekinase; determining the orientation of at least one such molecularscaffold in co-crystals with the kinase; identifying chemical structuresof one or more of the molecular scaffolds, that, when modified, alterthe binding affinity or binding specificity or both between themolecular scaffold and the kinase; and synthesizing a ligand in whichone or more of the chemical structures of the molecular scaffold ismodified to provide a ligand that binds to the kinase with alteredbinding affinity or binding specificity or both.

Reference to particular amino acid residues in human c-Kit polypeptideresidue number is defined by the numbering corresponding to the Kitsequence in GenBank NP_(—)000213 (SEQ ID NO:1). Reference to particularnucleotide positions in a nucleotide sequence encoding all or a portionof c-Kit is defined by the numbering corresponding to the sequenceprovided in GenBank NM_(—)000222 (SEQ ID NO:2).

The terms “Kit”, “c-Kit”, and “c-kit” mean an enzymatically activekinase that contains a portion with greater than 90% amino acid sequenceidentity to amino acid residues including the ATP binding site offull-length c-Kit (e.g., human c-Kit, e.g., the sequence NP_(—)000213),for a maximal alignment over an equal length segment; or that contains aportion with greater than 90% amino acid sequence identity to at least200 contiguous amino acids of native c-Kit and retains kinase activity.Preferably the sequence identity is at least 95, 97, 98, 99, or even100%. Preferably the specified level of sequence identity is over asequence at least 300 contiguous amino acid residues in length. Unlessindicated to the contrary, the term includes reference wild-type c-Kit,allelic variants, and mutated forms (e.g., having activating mutations).

The term “c-Kit kinase domain” refers to a reduced length c-Kit (i.e.,shorter than a full-length c-Kit by at least 50, at least 100, at least150, or at least 200, amino acids that includes the kinase catalyticregion in c-Kit. Highly preferably for use in this invention, the kinasedomain retains kinase activity, preferably at least 60, 70, 80, 90, or100% of the native c-Kit kinase activity.

As used herein, the terms “ligand” and “modulator” are used equivalentlyto refer to a compound that changes (i.e., increases or decreases) theactivity of a target biomolecule, e.g., an enzyme such as a kinase.Generally a ligand or modulator will be a small molecule, where “smallmolecule” refers to a compound with a molecular weight of 1500 daltonsor less, or preferably 1000 daltons or less, 800 daltons or less, or 600daltons or less. Thus, an “improved ligand” is one that possesses betterpharmacological and/or pharmacokinetic properties than a referencecompound, where “better” can be defined for a particular biologicalsystem or therapeutic use. In terms of the development of ligands fromscaffolds, a ligand is a derivative of a scaffold.

In the context of binding compounds, molecular scaffolds, and ligands,the term “derivative” or “derivative compound” refers to a compoundhaving a chemical structure that contains a common core chemicalstructure as a parent or reference compound, but differs by having atleast one structural difference, e.g., by having one or moresubstituents added and/or removed and/or substituted, and/or by havingone or more atoms substituted with different atoms. Unless clearlyindicated to the contrary, the term “derivative” does not mean that thederivative is synthesized using the parent compound as a startingmaterial or as an intermediate, although in some cases, the derivativemay be synthesized from the parent.

Thus, the term “parent compound” refers to a reference compound foranother compound, having structural features retained in the derivativecompound. Often but not always, a parent compound has a simpler chemicalstructure than the derivative.

By “chemical structure” or “chemical substructure” is meant anydefinable atom or group of atoms that constitute a part of a molecule.Normally, chemical substructures of a scaffold or ligand can have a rolein binding of the scaffold or ligand to a target molecule, or caninfluence the three-dimensional shape, electrostatic charge, and/orconformational properties of the scaffold or ligand.

The term “binds” in connection with the interaction between a target anda potential binding compound indicates that the potential bindingcompound associates with the target to a statistically significantdegree as compared to association with proteins generally (i.e.,non-specific binding). Thus, the term “binding compound” refers to acompound that has a statistically significant association with a targetmolecule. Preferably a binding compound interacts with a specifiedtarget with a dissociation constant (k_(d)) of 1 mM or less. A bindingcompound can bind with “low affinity”, “very low affinity”, “extremelylow affinity”, “moderate affinity”, “moderately high affinity”, or “highaffinity” as described herein.

In the context of compounds binding to a target, the term “greateraffinity” indicates that the compound binds more tightly than areference compound, or than the same compound in a reference condition,i.e., with a lower dissociation constant. In particular embodiments, thegreater affinity is at least 2, 3, 4, 5, 8, 10, 50, 100, 200, 400, 500,1000, or 10,000-fold greater affinity.

Also in the context of compounds binding to a biomolecular target, theterm “greater specificity” indicates that a compound binds to aspecified target to a greater extent than to another biomolecule orbiomolecules that may be present under relevant binding conditions,where binding to such other biomolecules produces a different biologicalactivity than binding to the specified target. Typically, thespecificity is with reference to a limited set of other biomolecules,e.g., in the case of c-Kit, other tyrosine kinases or even other type ofenzymes. In particular embodiments, the greater specificity is at least2, 3, 4, 5, 8, 10, 50, 100, 200, 400, 500, or 1000-fold greaterspecificity.

As used in connection with binding of a compound with a target, the term“interact” indicates that the distance from a bound compound to aparticular amino acid residue will be 5.0 angstroms or less. Inparticular embodiments, the distance from the compound to the particularamino acid residue is 4.5 angstroms or less, 4.0 angstroms or less, or3.5 angstroms or less. Such distances can be determined, for example,using co-crystallography, or estimated using computer fitting of acompound in an active site.

In a related aspect, the invention provides a method for developingligands specific for c-Kit, where the method involves determiningwhether a derivative of a compound of Formula I that binds to aplurality of kinases has greater specificity for that particular kinasethan the parent compound with respect to other kinases.

As used herein in connection with binding compounds or ligands, the term“specific for c-Kit kinase”, “specific for c-Kit” and terms of likeimport mean that a particular compound binds to c-Kit to a statisticallygreater extent than to other kinases that may be present in a particularorganism. Also, where biological activity other than binding isindicated, the term “specific for c-Kit” indicates that a particularcompound has greater biological effect associated with binding c-Kitthan to other tyrosine kinases, e.g., kinase activity inhibition.Preferably, the specificity is also with respect to other biomolecules(not limited to tyrosine kinases) that may be present within anorganism.

In another aspect, the invention provides a method for obtainingimproved ligands binding to c-Kit, where the method involves identifyinga compound of Formula I that binds to that particular kinase,determining whether that compound interacts with one or more conservedactive site residues, and determining whether a derivative of thatcompound binds to that kinase with greater affinity or greaterspecificity or both than the parent binding compound. Binding withgreater affinity or greater specificity or both than the parent compoundindicates that the derivative is an improved ligand. This process canalso be carried out in successive rounds of selection and derivatizationand/or with multiple parent compounds to provide a compound or compoundswith improved ligand characteristics. Likewise, the derivative compoundscan be tested and selected to give high selectivity for that kinase, orto give cross-reactivity to a particular set of targets, for example toa subset of kinases that includes c-Kit. In particular embodiments,known c-Kit inhibitors can be used, and derivatives with greateraffinity and/or greater specificity can be developed, preferably usingc-Kit structure information; greater specificity for c-Kit relative toother tyrosine kinases is developed.

By “molecular scaffold” or “scaffold” is meant a simple target bindingmolecule to which one or more additional chemical moieties can becovalently attached, modified, or eliminated to form a plurality ofmolecules with common structural elements. The moieties can include, butare not limited to, a halogen atom, a hydroxyl group, a methyl group, anitro group, a carboxyl group, or any other type of molecular groupincluding, but not limited to, those recited in this application.Molecular scaffolds bind to at least one target molecule, preferably toa plurality of molecules in a protein family, and the target moleculecan preferably be a enzyme, receptor, or other protein. Preferredcharacteristics of a scaffold can include binding at a target moleculebinding site such that one or more substituents on the scaffold aresituated in binding pockets in the target molecule binding site; havingchemically tractable structures that can be chemically modified,particularly by synthetic reactions, so that a combinatorial library canbe easily constructed; having chemical positions where moieties can beattached that do not interfere with binding of the scaffold to a proteinbinding site, such that the scaffold or library members can be modifiedto form ligands, to achieve additional desirable characteristics, e.g.,enabling the ligand to be actively transported into cells and/or tospecific organs, or enabling the ligand to be attached to achromatography column for additional analysis. Thus, a molecularscaffold is an identified target binding molecule prior to modificationto improve binding affinity and/or specificity, or other pharmacologicalproperties.

The term “scaffold core” refers to the core structure of a molecularscaffold onto which various substituents can be attached. Thus, for anumber of scaffold molecules of a particular chemical class, thescaffold core is common to all the scaffold molecules. In many cases,the scaffold core will consist of or include one or more ringstructures.

By “binding site” is meant an area of a target molecule to which aligand can bind non-covalently. Binding sites embody particular shapesand often contain multiple binding pockets present within the bindingsite. The particular shapes are often conserved within a class ofmolecules, such as a molecular family. Binding sites within a class alsocan contain conserved structures such as, for example, chemicalmoieties, the presence of a binding pocket, and/or an electrostaticcharge at the binding site or some portion of the binding site, all ofwhich can influence the shape of the binding site.

By “binding pocket” is meant a specific volume within a binding site. Abinding pocket can often be a particular shape, indentation, or cavityin the binding site. Binding pockets can contain particular chemicalgroups or structures that are important in the non-covalent binding ofanother molecule such as, for example, groups that contribute to ionic,hydrogen bonding, or van der Waals interactions between the molecules.

By “orientation”, in reference to a binding compound bound to a targetmolecule is meant the spatial relationship of the binding compound(which can be defined by reference to at least some of its consitituentatoms) to the binding pocket and/or atoms of the target molecule atleast partially defining the binding pocket.

In the context of target molecules in this invention, the term “crystal”refers to a regular assemblage of a target molecule of a type suitablefor X-ray crystallography. That is, the assemblage produces an X-raydiffraction pattern when illuminated with a beam of X-rays. Thus, acrystal is distinguished from an agglomeration or other complex oftarget molecule that does not give a diffraction pattern.

By “co-crystal” is meant a complex of the compound, molecular scaffold,or ligand bound non-covalently to the target molecule and present in acrystal form appropriate for analysis by X-ray or proteincrystallography. In preferred embodiments the target molecule-ligandcomplex can be a protein-ligand complex.

The phrase “alter the binding affinity or binding specificity” refers tochanging the binding constant of a first compound for another, orchanging the level of binding of a first compound for a second compoundas compared to the level of binding of the first compound for thirdcompounds, respectively. For example, the binding specificity of acompound for a particular protein is increased if the relative level ofbinding to that particular protein is increased as compared to bindingof the compound to unrelated proteins.

As used herein in connection with test compounds, binding compounds, andmodulators (ligands), the term “synthesizing” and like terms meanschemical synthesis from one or more precursor materials.

The phrase “chemical structure of the molecular scaffold is modified”means that a derivative molecule has a chemical structure that differsfrom that of the molecular scaffold but still contains common corechemical structural features. The phrase does not necessarily mean thatthe molecular scaffold is used as a precursor in the synthesis of thederivative.

By “assaying” is meant the creation of experimental conditions and thegathering of data regarding a particular result of the experimentalconditions. For example, enzymes can be assayed based on their abilityto act upon a detectable substrate. A compound or ligand can be assayedbased on its ability to bind to a particular target molecule ormolecules.

By a “set” of compounds is meant a collection of compounds. Thecompounds may or may not be structurally related.

As used herein, the term “azaindole scaffold” or azaindole scaffoldstructure” refers to the structure shown in Formula I. Similarly, theterm “azaindole core” refers to the structure shown above as Formula Iexcluding the R groups.

The invention further relates to co-crystals of c-Kit, which may be areduced length polypeptide, e.g., a kinase domain, and a c-Kit bindingcompound of Formula I or including the core structure of Formula I.Advantageously, such co-crystals are of sufficient size and quality toallow structural determination of the c-Kit to at least 3 Angstroms, 2.5Angstroms, 2.0 Angstroms, 1.8 Angstroms, 1.7 Angstroms, 1.5 Angstroms,1.4 Angstroms, 1.3 Angstroms, or 1.2 Angstroms. The co-crystals can, forexample, be in a crystallography plate, be mounted for X-raycrystallography and/or in an X-ray beam. Such co-crystals arebeneficial, for example, for obtaining structural information concerninginteraction between c-Kit and binding compounds.

Crystallization conditions can be initially identified using a screeningkit, such as a Hampton Research (Riverside, Calif.) screening kit 1.Conditions resulting in crystals can be selected and crystallizationconditions optimized based on the demonstrated crystallizationconditions. To assist in subsequent crystallography, the protein can beseleno-methionine labeled. Also, as indicated above, the protein may beany of various forms, e.g., truncated to provide a catalytic domain,which can be selected to be of various lengths.

In another aspect, provision of compounds of Formula I with activitytoward c-kit (such as compounds developed using methods describedherein) also provides a method for modulating the c-Kit activity bycontacting c-Kit with a compound of Formula I. The compound ispreferably provided at a level sufficient to modulate the activity ofthe c-Kit by at least 10%, more preferably at least 20%, 30%, 40%, or50%. In many embodiments, the compound will be at a concentration ofabout 1 μM, 100 μM, or 1 mM, or in a range of 1-100 nM, 100-500 nM,500-1000 nM, 1-100 μM, 100-500 μM, or 500-1000 μM. In particularembodiments, the contacting is carried out in vitro.

As used herein, the term “modulating” or “modulate” refers to an effectof altering a biological activity, especially a biological activityassociated with a particular biomolecule such as c-Kit. For example, anagonist or antagonist of a particular biomolecule modulates the activityof that biomolecule, e.g., an enzyme.

The term “c-Kit activity” refers to a biological activity of c-Kit,particularly including kinase activity.

In the context of the use, testing, or screening of compounds that areor may be modulators, the term “contacting” means that the compound(s)are caused to be in sufficient proximity to a particular molecule,complex, cell, tissue, organism, or other specified material thatpotential binding interactions and/or chemical reaction between thecompound and other specified material can occur.

As co-crystals of c-Kit have been developed and analyzed, another aspectrelates to an electronic representation of c-Kit (which may be a reducedlength c-Kit, usually a kinase domain), for example, an electronicrepresentation containing atomic coordinate representations for c-Kitcorresponding to the coordinates listed for c-Kit in Protein Data Bank(PDB) as 1 PDG or Molecular Modeling DataBase (MMDB) as 23938, modifiedby the replacement of STI-571 (Gleevec) with a compound of Formula I, ora schematic representation such as one showing secondary structureand/or chain folding, and may also show conserved active site residues.

The electronic representation can also be modified by replacingelectronic representations of particular residues with electronicrepresentations of other residues. Thus, for example, an electronicrepresentation containing atomic coordinate representationscorresponding to the coordinates for c-Kit listed in a database asindicated above can be modified by the replacement of coordinates for aparticular conserved residue in a binding site by a different aminoacid. Following a modification or modifications, the representation ofthe overall structure can be adjusted to allow for the knowninteractions that would be affected by the modification ormodifications. In most cases, a modification involving more than oneresidue will be performed in an iterative manner.

A binding site or catalytic domain can be represented in various ways,e.g., as representations of atomic coordinates of residues around thebinding site and/or as a binding site surface contour, and can includerepresentations of the binding character of particular residues at thebinding site, e.g., conserved residues.

In another aspect, the c-Kit structural information provides a methodfor developing useful biological agents based on c-Kit, by analyzing ac-Kit structure to identify at least one sub-structure for forming thebiological agent. Such sub-structures can include epitopes for antibodyformation, and the method includes developing antibodies against theepitopes, e.g., by injecting an epitope presenting composition in amammal such as a rabbit, guinea pig, pig, goat, or horse. Thesub-structure can also include a mutation site at which mutation isexpected to or is known to alter the activity of c-Kit, and the methodincludes creating a mutation at that site. Still further, thesub-structure can include an attachment point for attaching a separatemoiety, for example, a peptide, a polypeptide, a solid phase material(e.g., beads, gels, chromatographic media, slides, chips, plates, andwell surfaces), a linker, and a label (e.g., a direct label such as afluorophore or an indirect label, such as biotin or other member of aspecific binding pair). The method can include attaching the separatemoiety.

In another aspect, the invention provides a method for identifyingpotential c-Kit binding compounds by fitting at least one electronicrepresentation of a compound in an electronic representation of thec-Kit binding site. The representation of the binding site may be partof an electronic representation of a larger portion(s) or all of a c-Kitmolecule or may be a representation of only the catalytic domain or ofthe binding site or active site. The electronic representation may be asdescribed above or otherwise described herein.

In particular embodiments, the method involves fitting a computerrepresentation of a compound from a computer database with a computerrepresentation of the active site of the kinase, and involves removing acomputer representation of a compound complexed with the kinase moleculeand identifying compounds that best fit the active site based onfavorable geometric fit and energetically favorable complementaryinteractions as potential binding compounds. In particular embodiments,the compound is a known c-Kit inhibitor, e.g., as described in areference cited herein, or a derivative thereof.

In other embodiments, the method involves modifying a computerrepresentation of a compound complexed with the kinase molecule, by thedeletion or addition or both of one or more chemical groups; fitting acomputer representation of a compound from a computer database with acomputer representation of the active site of the kinase molecule; andidentifying compounds that best fit the active site based on favorablegeometric fit and energetically favorable complementary interactions aspotential binding compounds.

In still other embodiments, the method involves removing a computerrepresentation of a compound complexed with the kinase, and searching adatabase for compounds having structural similarity to the complexedcompound using a compound searching computer program or replacingportions of the complexed compound with similar chemical structuresusing a compound construction computer program.

Fitting a compound can include determining whether a compound willinteract with one or more conserved active site residues for the kinase.Compounds selected for fitting or that are complexed with the kinasecan, for example, be a known c-Kit inhibitor compound, or a compoundincluding the core structure of such compound.

In another aspect, the invention provides a method for attaching a c-Kitbinding compound to an attachment component, as well as a method foridentifying attachment sites on a c-Kit binding compound. The methodinvolves identifying energetically allowed sites for attachment of anattachment component for the binding compound bound to a binding site ofc-Kit; and attaching the compound or a derivative thereof to theattachment component at the energetically allowed site.

Attachment components can include, for example, linkers (includingtraceless linkers) for attachment to a solid phase or to anothermolecule or other moiety. Such attachment can be formed by synthesizingthe compound or derivative on the linker attached to a solid phasemedium e.g., in a combinatorial synthesis in a plurality of compound.Likewise, the attachment to a solid phase medium can provide an affinitymedium (e.g., for affinity chromatography).

The attachment component can also include a label, which can be adirectly detectable label such as a fluorophore, or an indirectlydetectable such as a member of a specific binding pair, e.g., biotin.

The ability to identify energetically allowed sites on a c-Kit bindingcompound, also, in a related aspect, provides modified binding compoundsthat have linkers attached, preferably at an energetically allowed sitefor binding of the modified compound to c-Kit. The linker can beattached to an attachment component as described above.

Another aspect of the present invention relates to a modified c-Kitpolypeptide that includes a modification that makes the modified c-Kitmore similar than native c-Kit to another tyrosine kinase, and can alsoinclude other mutations or other modifications. In various embodiments,the polypeptide includes a full-length c-Kit polypeptide, includes amodified c-Kit binding site, includes at least 20, 30, 40, 50, 60, 70,or 80 contiguous amino acid residues derived from c-Kit including aconserved site.

The invention also provides compounds that bind to and/or modulate(e.g., inhibit) c-Kit activity e.g., compounds identified by the methodsdescribed herein. Accordingly, in aspects and embodiments involvingc-Kit binding compounds, molecular scaffolds, and ligands or modulators,the compound is a weak binding compound; a moderate binding compound; astrong binding compound; the compound interacts with one or moreconserved active site residues in the kinase; the compound is a smallmolecule; the compound binds to a plurality of different kinases (e.g.,at least 2, 3, 4, 5, 7, 10, or more different kinases). In particular,the invention relates to compounds identified or selected using themethods described herein, or compounds of Formula I.

In the various aspects described above that involve atomic coordinatesfor c-Kit binding site in connection with binding compounds, thecoordinates provided in the listed databases can be used. Thosecoordinates can then be adjusted using conventional modeling methods tofit compounds having structures different from the compounds identifiedherein, and can thus be used for development of c-Kit modulatorsdifferent from currently described c-Kit modulators.

As used herein in connection with amino acid or nucleic acid sequence,the term “isolate” indicates that the sequence is separated from atleast a portion of the amino acid and/or nucleic acid sequences withwhich it would normally be associated.

In connection with amino acid or nucleic sequences, the term “purified”indicates that the particular molecule constitutes a significantlygreater proportion of the biomolecules in a composition than in a priorcomposition, e.g., in a cell culture. The greater proportion can be2-fold, 5-fold, 10-fold or more greater.

Additional aspects and embodiments will be apparent from the followingDetailed Description and from the claims.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS I. General

The present invention provides compounds of Formula I that areinhibitors of c-Kit, and the use of models of the binding site of c-Kit,structural information, and related compositions for developing improvedcompounds with those structures that modulate c-Kit activity.

Table 1 provides the structures and names of a set of exemplarycompounds of Formula I with activity toward c-kit.

Table 2 provides descriptions of additional exemplary compounds ofFormula I.

Exemplary compounds of Formula I active against c-kit are shown in Table1.

TABLE 1 Table Cmpd Cmpd # Structure Name MW 1-1 9

benzyl-[5-(1H- pyrrolo[2,3-b]pyridin-3- ylmethyl)-pyridin-2-yl]- amine315 1-2 11

(6-Benzylamino-pyridin- 3-yl)-(1H-pyrrolo[2,3- b]pyridin-3-yl)-methanone 329 1-3 12

[5-(1H-Pyrrolo[2,3- b]pyridin-3-ylmethyl)- pyridin-2-yl]-(4-trifluoromethyl-benzyl)- amine 383 1-4 15

(4-methoxy-benzyl)-[5- (1H-pyrrolo[2,3- b]pyridin-3-ylmethyl)-pyridin-2-yl]-amine 344.4 1-5 16

(4-chloro-benzyl)-[5-(1H- pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]- amine 348.8 1-6 17

(4-fluoro-benzyl)-[5-(1H- pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]- amine 332.4 1-7 18

(4-methyl-benzyl)-[5- (1H-pyrrolo[2,3- b]pyridin-3-ylmethyl)-pyridin-2-yl]-amine 328.4 1-8 19

[5-(1H-pyrrolo[2,3- b]pyridin-3-ylmethyl)- pyridin-2-yl]-thiophen-2-ylmethyl-amine 330.4

Additional exemplary compounds of Formula I are described in Table 2 bydescribing the moieties present in the following sub-generic structureof Formula I. In this sub-generic structure, L¹ is a non-cyclic linkerwith 1-3 linked atoms connecting C¹ with the bi-cyclic core (notcounting any side groups or atoms); C¹ is cyclic group, preferably anaryl or heteroaryl group, L² is a non-cyclic linker with 1-4 linkedatoms connecting C¹ and C² (not counting any side groups or atoms);Z_(p) represents p non-hydrogen substituents on C², where p is 0-4 andeach Z may be the same or different.

TABLE 2

L¹ C¹ L² C² Z CH₂ pyridinyl NH—CH₂ Phenyl None CH₂ pyridinyl NH—CH₂Phenyl Z₁: F (para) CH₂ pyridinyl NH—CH₂ Phenyl Z₁: F (meta) CH₂pyridinyl NH—CH₂ Phenyl Z₁: F (ortho) CH₂ pyridinyl NH—CH₂ Phenyl Z₁: F(para) Z₂: F (meta) CH₂ Pyridinyl NH—CH₂ Phenyl Z₁: Cl (meta) CH₂Pyridinyl NH—CH₂ Phenyl Z₁: Cl (para) CH₂ Pyridinyl NH—CH₂ Phenyl Z₁: Cl(para) Z₂: Cl (meta) CH₂ Pyridinyl NH—CH₂ Phenyl Z₁: F (para) Z₂: Cl(meta) CH₂ Pyridinyl NH—CH₂ Phenyl Z₁: Cl (para) Z₂: F (meta) CH₂Pyridinyl NH—CH₂ Phenyl Z₁: CH₃ (para) CH₂ Pyridinyl NH—CH₂ Phenyl Z₁:CH₃ (meta) CH₂ Pyridinyl NH—CH₂ Phenyl Z₁: CH₃ (ortho) CH₂ PyridinylNH—CH₂ Phenyl Z₁: CH₂—CH₃ (para) CH₂ Pyridinyl NH—CH₂ Phenyl Z₁: CH₂—CH₃(meta) CH₂ Pyridinyl NH—CH₂ Phenyl Z₁: CH₂—CH₃ (ortho) CH₂ PyridinylNH—CH₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CH₂ Pyridinyl NH—CH₂ PhenylZ₁: CH₂—CH₂—CH₃ or iPr (meta) CH₂ Pyridinyl NH—CH₂ Phenyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyridinyl NH—CH₂ Phenyl Z₁: CH₂F (para)CH₂ Pyridinyl NH—CH₂ Phenyl Z₁: CH₂F (meta) CH₂ Pyridinyl NH—CH₂ PhenylZ₁: CH₂F (ortho) CH₂ Pyridinyl NH—CH₂ Phenyl Z₁: CHF₂ (para) CH₂Pyridinyl NH—CH₂ Phenyl Z₁: CHF₂ (meta) CH₂ Pyridinyl NH—CH₂ Phenyl Z₁:CHF₂ (ortho) CH₂ Pyridinyl NH—CH₂ Phenyl Z₁: CF₃ (para) CH₂ PyridinylNH—CH₂ Phenyl Z₁: CF₃ (meta) CH₂ Pyridinyl NH—CH₂ Phenyl Z₁: CF₃ (ortho)CH₂ Pyridinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂F (para) CH₂ Pyridinyl NH—CH₂Phenyl Z₁: CH₂—CH₂F (meta) CH₂ Pyridinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂F(ortho) CH₂ Pyridinyl NH—CH₂ Phenyl Z₁: CH₂—CHF₂ (para) CH₂ PyridinylNH—CH₂ Phenyl Z₁: CH₂—CHF₂ (meta) CH₂ Pyridinyl NH—CH₂ Phenyl Z₁:CH₂—CHF₂ (ortho) CH₂ Pyridinyl NH—CH₂ Phenyl Z₁: CH₂—CF₃ (para) CH₂Pyridinyl NH—CH₂ Phenyl Z₁: CH₂—CF₃ (meta) CH₂ Pyridinyl NH—CH₂ PhenylZ₁: CH₂—CF₃ (ortho) CH₂ pyridinyl NH—CH₂ Pyridinyl None CH₂ pyridinylNH—CH₂ Pyridinyl Z₁: F (para) CH₂ pyridinyl NH—CH₂ Pyridinyl Z₁: F(meta) CH₂ pyridinyl NH—CH₂ Pyridinyl Z₁: F (ortho) CH₂ pyridinyl NH—CH₂Pyridinyl Z₁: F (para) Z₂: F (meta) CH₂ Pyridinyl NH—CH₂ Pyridinyl Z₁:Cl (meta) CH₂ Pyridinyl NH—CH₂ Pyridinyl Z₁: Cl (para) CH₂ PyridinylNH—CH₂ Pyridinyl Z₁: Cl (para) Z₂: Cl (meta) CH₂ Pyridinyl NH—CH₂Pyridinyl Z₁: F (para) Z₂: Cl (meta) CH₂ Pyridinyl NH—CH₂ Pyridinyl Z₁:Cl (para) Z₂: F (meta) CH₂ Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₃ (para) CH₂Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₃ (meta) CH₂ Pyridinyl NH—CH₂ PyridinylZ₁: CH₃ (ortho) CH₂ Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₃ (para) CH₂Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₃ (meta) CH₂ Pyridinyl NH—CH₂Pyridinyl Z₁: CH₂—CH₃ (ortho) CH₂ Pyridinyl NH—CH₂ Pyridinyl Z₁:CH₂—CH₂—CH₃ or iPr (para) CH₂ Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₂—CH₃or iPr (meta) CH₂ Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₂—CH₃ oriPr(ortho) CH₂ Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₂F (para) CH₂ PyridinylNH—CH₂ Pyridinyl Z₁: CH₂F (meta) CH₂ Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₂F(ortho) CH₂ Pyridinyl NH—CH₂ Pyridinyl Z₁: CHF₂ (para) CH₂ PyridinylNH—CH₂ Pyridinyl Z₁: CHF₂ (meta) CH₂ Pyridinyl NH—CH₂ Pyridinyl Z₁: CHF₂(ortho) CH₂ Pyridinyl NH—CH₂ Pyridinyl Z₁: CF₃ (para) CH₂ PyridinylNH—CH₂ Pyridinyl Z₁: CF₃ (meta) CH₂ Pyridinyl NH—CH₂ Pyridinyl Z₁: CF₃(ortho) CH₂ Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₂F (para) CH₂ PyridinylNH—CH₂ Pyridinyl Z₁: CH₂—CH₂F (meta) CH₂ Pyridinyl NH—CH₂ Pyridinyl Z₁:CH₂—CH₂F (ortho) CH₂ Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₂—CHF₂ (para) CH₂Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₂—CHF₂ (meta) CH₂ Pyridinyl NH—CH₂Pyridinyl Z₁: CH₂—CHF₂ (ortho) CH₂ Pyridinyl NH—CH₂ Pyridinyl Z₁:CH₂—CF₃ (para) CH₂ Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₂—CF₃ (meta) CH₂Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₂—CF₃ (ortho) CH₂ pyridinyl NH—CH₂Pyrimidinyl None CH₂ pyridinyl NH—CH₂ Pyrimidinyl Z₁: F (para) CH₂pyridinyl NH—CH₂ Pyrimidinyl Z₁: F (meta) CH₂ pyridinyl NH—CH₂Pyrimidinyl Z₁: F (ortho) CH₂ pyridinyl NH—CH₂ Pyrimidinyl Z₁: F (para)Z₂: F (meta) CH₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁: Cl (meta) CH₂Pyridinyl NH—CH₂ Pyrimidinyl Z₁: Cl (para) CH₂ Pyridinyl NH—CH₂Pyrimidinyl Z₁: Cl (para) Z₂: Cl (meta) CH₂ Pyridinyl NH—CH₂ PyrimidinylZ₁: F (para) Z₂: Cl (meta) CH₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁: Cl(para) Z₂: F (meta) CH₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₃ (para) CH₂Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₃ (meta) CH₂ Pyridinyl NH—CH₂Pyrimidinyl Z₁: CH₃ (ortho) CH₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₃(para) CH₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₃ (meta) CH₂ PyridinylNH—CH₂ Pyrimidinyl Z₁: CH₂—CH₃ (ortho) CH₂ Pyridinyl NH—CH₂ PyrimidinylZ₁: CH₂—CH₂—CH₃ or iPr (para) CH₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) CH₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₂F(para) CH₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₂F (meta) CH₂ PyridinylNH—CH₂ Pyrimidinyl Z₁: CH₂F (ortho) CH₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁:CHF₂ (para) CH₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CHF₂ (meta) CH₂Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CHF₂ (ortho) CH₂ Pyridinyl NH—CH₂Pyrimidinyl Z₁: CF₃ (para) CH₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CF₃(meta) CH₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CF₃ (ortho) CH₂ PyridinylNH—CH₂ Pyrimidinyl Z₁: CH₂—CH₂F (para) CH₂ Pyridinyl NH—CH₂ PyrimidinylZ₁: CH₂—CH₂F (meta) CH₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₂F(ortho) CH₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CHF₂ (para) CH₂Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CHF₂ (meta) CH₂ Pyridinyl NH—CH₂Pyrimidinyl Z₁: CH₂—CHF₂ (ortho) CH₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁:CH₂—CF₃ (para) CH₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CF₃ (meta) CH₂Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CF₃ (ortho) CH₂ pyridinyl NH—CH₂Pyrazinyl None CH₂ pyridinyl NH—CH₂ Pyrazinyl Z₁: F (para) CH₂ pyridinylNH—CH₂ Pyrazinyl Z₁: F (meta) CH₂ pyridinyl NH—CH₂ Pyrazinyl Z₁: F(ortho) CH₂ pyridinyl NH—CH₂ Pyrazinyl Z₁: F (para) Z₂: F (meta) CH₂Pyridinyl NH—CH₂ Pyrazinyl Z₁: Cl (meta) CH₂ Pyridinyl NH—CH₂ PyrazinylZ₁: Cl (para) CH₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁: Cl (para) Z₂: Cl (meta)CH₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁: F (para) Z₂: Cl (meta) CH₂ PyridinylNH—CH₂ Pyrazinyl Z₁: Cl (para) Z₂: F (meta) CH₂ Pyridinyl NH—CH₂Pyrazinyl Z₁: CH₃ (para) CH₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₃ (meta)CH₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₃ (ortho) CH₂ Pyridinyl NH—CH₂Pyrazinyl Z₁: CH₂—CH₃ (para) CH₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₃(meta) CH₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₃ (ortho) CH₂ PyridinylNH—CH₂ Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CH₂ Pyridinyl NH—CH₂Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CH₂ Pyridinyl NH—CH₂ PyrazinylZ₁: CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂F(para) CH₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂F (meta) CH₂ PyridinylNH—CH₂ Pyrazinyl Z₁: CH₂F (ortho) CH₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁:CHF₂ (para) CH₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁: CHF₂ (meta) CH₂ PyridinylNH—CH₂ Pyrazinyl Z₁: CHF₂ (ortho) CH₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁: CF₃(para) CH₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁: CF₃ (meta) CH₂ PyridinylNH—CH₂ Pyrazinyl Z₁: CF₃ (ortho) CH₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁:CH₂—CH₂F (para) CH₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₂F (meta) CH₂Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₂F (ortho) CH₂ Pyridinyl NH—CH₂Pyrazinyl Z₁: CH₂—CHF₂ (para) CH₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁:CH₂—CHF₂ (meta) CH₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CHF₂ (ortho) CH₂Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CF₃ (para) CH₂ Pyridinyl NH—CH₂Pyrazinyl Z₁: CH₂—CF₃ (meta) CH₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CF₃(ortho) CH₂ pyridinyl NH—CH₂ Pyrrolyl None CH₂ pyridinyl NH—CH₂ PyrrolylZ₁: F (2) CH₂ pyridinyl NH—CH₂ Pyrrolyl Z₁: F (3) CH₂ pyridinyl NH—CH₂Pyrrolyl Z₁: F (2) Z₂: F (3) CH₂ Pyridinyl NH—CH₂ Pyrrolyl Z₁: Cl (2)CH₂ Pyridinyl NH—CH₂ Pyrrolyl Z₁: Cl (3) CH₂ Pyridinyl NH—CH₂ PyrrolylZ₁: Cl (2) Z₂: Cl (3) CH₂ Pyridinyl NH—CH₂ Pyrrolyl Z₁: F (2) Z₂: Cl (3)CH₂ Pyridinyl NH—CH₂ Pyrrolyl Z₁: Cl (2) Z₂: F (3) CH₂ Pyridinyl NH—CH₂Pyrrolyl Z₁: CH₃ (2) CH₂ Pyridinyl NH—CH₂ Pyrrolyl Z₁: CH₃ (3) CH₂Pyridinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₃ (2) CH₂ Pyridinyl NH—CH₂ PyrrolylZ₁: CH₂—CH₃ (3) CH₂ Pyridinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (2)CH₂ Pyridinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CH₂ PyridinylNH—CH₂ Pyrrolyl Z₁: CH₂F (2) CH₂ Pyridinyl NH—CH₂ Pyrrolyl Z₁: CH₂F (3)CH₂ Pyridinyl NH—CH₂ Pyrrolyl Z₁: CHF₂ (2) CH₂ Pyridinyl NH—CH₂ PyrrolylZ₁: CHF₂ (3) CH₂ Pyridinyl NH—CH₂ Pyrrolyl Z₁: CF₃ (2) CH₂ PyridinylNH—CH₂ Pyrrolyl Z₁: CF₃ (3) CH₂ Pyridinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₂F(2) CH₂ Pyridinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₂F (3) CH₂ Pyridinyl NH—CH₂Pyrrolyl Z₁: CH₂—CHF₂ (2) CH₂ Pyridinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CHF₂ (3)CH₂ Pyridinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CF₃ (2) CH₂ Pyridinyl NH—CH₂Pyrrolyl Z₁: CH₂—CF₃ (3) CH₂ pyridinyl NH—CH₂ Imidazolyl None CH₂pyridinyl NH—CH₂ Imidazolyl Z₁: F (2) CH₂ pyridinyl NH—CH₂ ImidazolylZ₁: F (3) CH₂ pyridinyl NH—CH₂ Imidazolyl Z₁: F (2) Z₂: F (3) CH₂Pyridinyl NH—CH₂ Imidazolyl Z₁: Cl (2) CH₂ Pyridinyl NH—CH₂ ImidazolylZ₁: Cl (3) CH₂ Pyridinyl NH—CH₂ Imidazolyl Z₁: Cl (2) Z₂: Cl (3) CH₂Pyridinyl NH—CH₂ Imidazolyl Z₁: F (2) Z₂: Cl (3) CH₂ Pyridinyl NH—CH₂Imidazolyl Z₁: Cl (2) Z₂: F (3) CH₂ Pyridinyl NH—CH₂ Imidazolyl Z₁: CH₃(2) CH₂ Pyridinyl NH—CH₂ Imidazolyl Z₁: CH₃ (3) CH₂ Pyridinyl NH—CH₂Imidazolyl Z₁: CH₂—CH₃ (2) CH₂ Pyridinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₃(3) CH₂ Pyridinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂Pyridinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CH₂ PyridinylNH—CH₂ Imidazolyl Z₁: CH₂F (2) CH₂ Pyridinyl NH—CH₂ Imidazolyl Z₁: CH₂F(3) CH₂ Pyridinyl NH—CH₂ Imidazolyl Z₁: CHF₂ (2) CH₂ Pyridinyl NH—CH₂Imidazolyl Z₁: CHF₂ (3) CH₂ Pyridinyl NH—CH₂ Imidazolyl Z₁: CF₃ (2) CH₂Pyridinyl NH—CH₂ Imidazolyl Z₁: CF₃ (3) CH₂ Pyridinyl NH—CH₂ ImidazolylZ₁: CH₂—CH₂F (2) CH₂ Pyridinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₂F (3) CH₂Pyridinyl NH—CH₂ Imidazolyl Z₁: CH₂—CHF₂ (2) CH₂ Pyridinyl NH—CH₂Imidazolyl Z₁: CH₂—CHF₂ (3) CH₂ Pyridinyl NH—CH₂ Imidazolyl Z₁: CH₂—CF₃(2) CH₂ Pyridinyl NH—CH₂ Imidazolyl Z₁: CH₂—CF₃ (3) CH₂ pyridinyl NH—CH₂Furanyl None CH₂ pyridinyl NH—CH₂ Furanyl Z₁: F (2) CH₂ pyridinyl NH—CH₂Furanyl Z₁: F (3) CH₂ pyridinyl NH—CH₂ Furanyl Z₁: F (2) Z₂: F (3) CH₂Pyridinyl NH—CH₂ Furanyl Z₁: Cl (2) CH₂ Pyridinyl NH—CH₂ Furanyl Z₁: Cl(3) CH₂ Pyridinyl NH—CH₂ Furanyl Z₁: Cl (2) Z₂: Cl (3) CH₂ PyridinylNH—CH₂ Furanyl Z₁: F (2) Z₂: Cl (3) CH₂ Pyridinyl NH—CH₂ Furanyl Z₁: Cl(2) Z₂: F (3) CH₂ Pyridinyl NH—CH₂ Furanyl Z₁: CH₃ (2) CH₂ PyridinylNH—CH₂ Furanyl Z₁: CH₃ (3) CH₂ Pyridinyl NH—CH₂ Furanyl Z₁: CH₂—CH₃ (2)CH₂ Pyridinyl NH—CH₂ Furanyl Z₁: CH₂—CH₃ (3) CH₂ Pyridinyl NH—CH₂Furanyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂ Pyridinyl NH—CH₂ Furanyl Z₁:CH₂—CH₂—CH₃ or iPr (3) CH₂ Pyridinyl NH—CH₂ Furanyl Z₁: CH₂F (2) CH₂Pyridinyl NH—CH₂ Furanyl Z₁: CH₂F (3) CH₂ Pyridinyl NH—CH₂ Furanyl Z₁:CHF₂ (2) CH₂ Pyridinyl NH—CH₂ Furanyl Z₁: CHF₂ (3) CH₂ Pyridinyl NH—CH₂Furanyl Z₁: CF₃ (2) CH₂ Pyridinyl NH—CH₂ Furanyl Z₁: CF₃ (3) CH₂Pyridinyl NH—CH₂ Furanyl Z₁: CH₂—CH₂F (2) CH₂ Pyridinyl NH—CH₂ FuranylZ₁: CH₂—CH₂F (3) CH₂ Pyridinyl NH—CH₂ Furanyl Z₁: CH₂—CHF₂ (2) CH₂Pyridinyl NH—CH₂ Furanyl Z₁: CH₂—CHF₂ (3) CH₂ Pyridinyl NH—CH₂ FuranylZ₁: CH₂—CF₃ (2) CH₂ Pyridinyl NH—CH₂ Furanyl Z₁: CH₂—CF₃ (3) CH₂pyridinyl NH—CH₂ Oxazolyl None CH₂ pyridinyl NH—CH₂ Oxazolyl Z₁: F (2)CH₂ pyridinyl NH—CH₂ Oxazolyl Z₁: F (3) CH₂ pyridinyl NH—CH₂ OxazolylZ₁: F (2) Z₂: F (3) CH₂ Pyridinyl NH—CH₂ Oxazolyl Z₁: Cl (2) CH₂Pyridinyl NH—CH₂ Oxazolyl Z₁: Cl (3) CH₂ Pyridinyl NH—CH₂ Oxazolyl Z₁:Cl (2) Z₂: Cl (3) CH₂ Pyridinyl NH—CH₂ Oxazolyl Z₁: F (2) Z₂: Cl (3) CH₂Pyridinyl NH—CH₂ Oxazolyl Z₁: Cl (2) Z₂: F (3) CH₂ Pyridinyl NH—CH₂Oxazolyl Z₁: CH₃ (2) CH₂ Pyridinyl NH—CH₂ Oxazolyl Z₁: CH₃ (3) CH₂Pyridinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₃ (2) CH₂ Pyridinyl NH—CH₂ OxazolylZ₁: CH₂—CH₃ (3) CH₂ Pyridinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2)CH₂ Pyridinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CH₂ PyridinylNH—CH₂ Oxazolyl Z₁: CH₂F (2) CH₂ Pyridinyl NH—CH₂ Oxazolyl Z₁: CH₂F (3)CH₂ Pyridinyl NH—CH₂ Oxazolyl Z₁: CHF₂ (2) CH₂ Pyridinyl NH—CH₂ OxazolylZ₁: CHF₂ (3) CH₂ Pyridinyl NH—CH₂ Oxazolyl Z₁: CF₃ (2) CH₂ PyridinylNH—CH₂ Oxazolyl Z₁: CF₃ (3) CH₂ Pyridinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₂F(2) CH₂ Pyridinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₂F (3) CH₂ Pyridinyl NH—CH₂Oxazolyl Z₁: CH₂—CHF₂ (2) CH₂ Pyridinyl NH—CH₂ Oxazolyl Z₁: CH₂—CHF₂ (3)CH₂ Pyridinyl NH—CH₂ Oxazolyl Z₁: CH₂—CF₃ (2) CH₂ Pyridinyl NH—CH₂Oxazolyl Z₁: CH₂—CF₃ (3) CH₂ pyridinyl NH—CH₂ Thiophenyl None CH₂pyridinyl NH—CH₂ Thiophenyl Z₁: F (2) CH₂ pyridinyl NH—CH₂ ThiophenylZ₁: F (3) CH₂ pyridinyl NH—CH₂ Thiophenyl Z₁: F (2) Z₂: F (3) CH₂Pyridinyl NH—CH₂ Thiophenyl Z₁: Cl (2) CH₂ Pyridinyl NH—CH₂ ThiophenylZ₁: Cl (3) CH₂ Pyridinyl NH—CH₂ Thiophenyl Z₁: Cl (2) Z₂: Cl (3) CH₂Pyridinyl NH—CH₂ Thiophenyl Z₁: F (2) Z₂: Cl (3) CH₂ Pyridinyl NH—CH₂Thiophenyl Z₁: Cl (2) Z₂: F (3) CH₂ Pyridinyl NH—CH₂ Thiophenyl Z₁: CH₃(2) CH₂ Pyridinyl NH—CH₂ Thiophenyl Z₁: CH₃ (3) CH₂ Pyridinyl NH—CH₂Thiophenyl Z₁: CH₂—CH₃ (2) CH₂ Pyridinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₃(3) CH₂ Pyridinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂Pyridinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CH₂ PyridinylNH—CH₂ Thiophenyl Z₁: CH₂F (2) CH₂ Pyridinyl NH—CH₂ Thiophenyl Z₁: CH₂F(3) CH₂ Pyridinyl NH—CH₂ Thiophenyl Z₁: CHF₂ (2) CH₂ Pyridinyl NH—CH₂Thiophenyl Z₁: CHF₂ (3) CH₂ Pyridinyl NH—CH₂ Thiophenyl Z₁: CF₃ (2) CH₂Pyridinyl NH—CH₂ Thiophenyl Z₁: CF₃ (3) CH₂ Pyridinyl NH—CH₂ ThiophenylZ₁: CH₂—CH₂F (2) CH₂ Pyridinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₂F (3) CH₂Pyridinyl NH—CH₂ Thiophenyl Z₁: CH₂—CHF₂ (2) CH₂ Pyridinyl NH—CH₂Thiophenyl Z₁: CH₂—CHF₂ (3) CH₂ Pyridinyl NH—CH₂ Thiophenyl Z₁: CH₂—CF₃(2) CH₂ Pyridinyl NH—CH₂ Thiophenyl Z₁: CH₂—CF₃ (3) CH₂ pyridinyl NH—CH₂Thiazolyl None CH₂ pyridinyl NH—CH₂ Thiazolyl Z₁: F (2) CH₂ pyridinylNH—CH₂ Thiazolyl Z₁: F (3) CH₂ pyridinyl NH—CH₂ Thiazolyl Z₁: F (2) Z₂:F (3) CH₂ Pyridinyl NH—CH₂ Thiazolyl Z₁: Cl (2) CH₂ Pyridinyl NH—CH₂Thiazolyl Z₁: Cl (3) CH₂ Pyridinyl NH—CH₂ Thiazolyl Z₁: Cl (2) Z₂: Cl(3) CH₂ Pyridinyl NH—CH₂ Thiazolyl Z₁: F (2) Z₂: Cl (3) CH₂ PyridinylNH—CH₂ Thiazolyl Z₁: Cl (2) Z₂: F (3) CH₂ Pyridinyl NH—CH₂ Thiazolyl Z₁:CH₃ (2) CH₂ Pyridinyl NH—CH₂ Thiazolyl Z₁: CH₃ (3) CH₂ Pyridinyl NH—CH₂Thiazolyl Z₁: CH₂—CH₃ (2) CH₂ Pyridinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₃ (3)CH₂ Pyridinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂ PyridinylNH—CH₂ Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CH₂ Pyridinyl NH—CH₂Thiazolyl Z₁: CH₂F (2) CH₂ Pyridinyl NH—CH₂ Thiazolyl Z₁: CH₂F (3) CH₂Pyridinyl NH—CH₂ Thiazolyl Z₁: CHF₂ (2) CH₂ Pyridinyl NH—CH₂ ThiazolylZ₁: CHF₂ (3) CH₂ Pyridinyl NH—CH₂ Thiazolyl Z₁: CF₃ (2) CH₂ PyridinylNH—CH₂ Thiazolyl Z₁: CF₃ (3) CH₂ Pyridinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₂F(2) CH₂ Pyridinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₂F (3) CH₂ Pyridinyl NH—CH₂Thiazolyl Z₁: CH₂—CHF₂ (2) CH₂ Pyridinyl NH—CH₂ Thiazolyl Z₁: CH₂—CHF₂(3) CH₂ Pyridinyl NH—CH₂ Thiazolyl Z₁: CH₂—CF₃ (2) CH₂ Pyridinyl NH—CH₂Thiazolyl Z₁: CH₂—CF₃ (3) CH₂ pyridinyl NH—C(O) Phenyl None CH₂pyridinyl NH—C(O) Phenyl Z₁: F (para) CH₂ pyridinyl NH—C(O) phenyl Z₁: F(meta) CH₂ pyridinyl NH—C(O) phenyl Z₁: F (ortho) CH₂ pyridinyl NH—C(O)phenyl Z₁: F (para) Z₂: F (meta) CH₂ Pyridinyl NH—C(O) Phenyl Z₁: Cl(meta) CH₂ Pyridinyl NH—C(O) Phenyl Z₁: Cl (para) CH₂ Pyridinyl NH—C(O)Phenyl Z₁: Cl (para) Z₂: Cl (meta) CH₂ Pyridinyl NH—C(O) Phenyl Z₁: F(para) Z₂: Cl (meta) CH₂ Pyridinyl NH—C(O) Phenyl Z₁: Cl (para) Z₂: F(meta) CH₂ Pyridinyl NH—C(O) Phenyl Z₁: CH₃ (para) CH₂ Pyridinyl NH—C(O)Phenyl Z₁: CH₃ (meta) CH₂ Pyridinyl NH—C(O) Phenyl Z₁: CH₃ (ortho) CH₂Pyridinyl NH—C(O) Phenyl Z₁: CH₂—CH₃ (para) CH₂ Pyridinyl NH—C(O) PhenylZ₁: CH₂—CH₃ (meta) CH₂ Pyridinyl NH—C(O) Phenyl Z₁: CH₂—CH₃ (ortho) CH₂Pyridinyl NH—C(O) Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CH₂ PyridinylNH—C(O) Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CH₂ Pyridinyl NH—C(O)Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyridinyl NH—C(O) Phenyl Z₁:CH₂F (para) CH₂ Pyridinyl NH—C(O) Phenyl Z₁: CH₂F (meta) CH₂ PyridinylNH—C(O) Phenyl Z₁: CH₂F (ortho) CH₂ Pyridinyl NH—C(O) Phenyl Z₁: CHF₂(para) CH₂ Pyridinyl NH—C(O) Phenyl Z₁: CHF₂ (meta) CH₂ PyridinylNH—C(O) Phenyl Z₁: CHF₂ (ortho) CH₂ Pyridinyl NH—C(O) Phenyl Z₁: CF₃(para) CH₂ Pyridinyl NH—C(O) Phenyl Z₁: CF₃ (meta) CH₂ Pyridinyl NH—C(O)Phenyl Z₁: CF₃ (ortho) CH₂ Pyridinyl NH—C(O) Phenyl Z₁: CH₂—CH₂F (para)CH₂ Pyridinyl NH—C(O) Phenyl Z₁: CH₂—CH₂F (meta) CH₂ Pyridinyl NH—C(O)Phenyl Z₁: CH₂—CH₂F (ortho) CH₂ Pyridinyl NH—C(O) Phenyl Z₁: CH₂—CHF₂(para) CH₂ Pyridinyl NH—C(O) Phenyl Z₁: CH₂—CHF₂ (meta) CH₂ PyridinylNH—C(O) Phenyl Z₁: CH₂—CHF₂ (ortho) CH₂ Pyridinyl NH—C(O) Phenyl Z₁:CH₂—CF₃ (para) CH₂ Pyridinyl NH—C(O) Phenyl Z₁: CH₂—CF₃ (meta) CH₂Pyridinyl NH—C(O) Phenyl Z₁: CH₂—CF₃ (ortho) CH₂ pyridinyl NH—C(O)Pyridinyl None CH₂ pyridinyl NH—C(O) Pyridinyl Z₁: F (para) CH₂pyridinyl NH—C(O) Pyridinyl Z₁: F (meta) CH₂ pyridinyl NH—C(O) PyridinylZ₁: F (ortho) CH₂ pyridinyl NH—C(O) Pyridinyl Z₁: F (para) Z₂: F (meta)CH₂ Pyridinyl NH—C(O) Pyridinyl Z₁: Cl (meta) CH₂ Pyridinyl NH—C(O)Pyridinyl Z₁: Cl (para) CH₂ Pyridinyl NH—C(O) Pyridinyl Z₁: Cl (para)Z₂: Cl (meta) CH₂ Pyridinyl NH—C(O) Pyridinyl Z₁: F (para) Z₂: Cl (meta)CH₂ Pyridinyl NH—C(O) Pyridinyl Z₁: Cl (para) Z₂: F (meta) CH₂ PyridinylNH—C(O) Pyridinyl Z₁: CH₃ (para) CH₂ Pyridinyl NH—C(O) Pyridinyl Z₁: CH₃(meta) CH₂ Pyridinyl NH—C(O) Pyridinyl Z₁: CH₃ (ortho) CH₂ PyridinylNH—C(O) Pyridinyl Z₁: CH₂—CH₃ (para) CH₂ Pyridinyl NH—C(O) Pyridinyl Z₁:CH₂—CH₃ (meta) CH₂ Pyridinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₃ (ortho) CH₂Pyridinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CH₂ PyridinylNH—C(O) Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CH₂ Pyridinyl NH—C(O)Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyridinyl NH—C(O) PyridinylZ₁: CH₂F (para) CH₂ Pyridinyl NH—C(O) Pyridinyl Z₁: CH₂F (meta) CH₂Pyridinyl NH—C(O) Pyridinyl Z₁: CH₂F (ortho) CH₂ Pyridinyl NH—C(O)Pyridinyl Z₁: CHF₂ (para) CH₂ Pyridinyl NH—C(O) Pyridinyl Z₁: CHF₂(meta) CH₂ Pyridinyl NH—C(O) Pyridinyl Z₁: CHF₂ (ortho) CH₂ PyridinylNH—C(O) Pyridinyl Z₁: CF₃ (para) CH₂ Pyridinyl NH—C(O) Pyridinyl Z₁: CF₃(meta) CH₂ Pyridinyl NH—C(O) Pyridinyl Z₁: CF₃ (ortho) CH₂ PyridinylNH—C(O) Pyridinyl Z₁: CH₂—CH₂F (para) CH₂ Pyridinyl NH—C(O) PyridinylZ₁: CH₂—CH₂F (meta) CH₂ Pyridinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₂F (ortho)CH₂ Pyridinyl NH—C(O) Pyridinyl Z₁: CH₂—CHF₂ (para) CH₂ PyridinylNH—C(O) Pyridinyl Z₁: CH₂—CHF₂ (meta) CH₂ Pyridinyl NH—C(O) PyridinylZ₁: CH₂—CHF₂ (ortho) CH₂ Pyridinyl NH—C(O) Pyridinyl Z₁: CH₂—CF₃ (para)CH₂ Pyridinyl NH—C(O) Pyridinyl Z₁: CH₂—CF₃ (meta) CH₂ Pyridinyl NH—C(O)Pyridinyl Z₁: CH₂—CF₃ (ortho) CH₂ pyridinyl NH—C(O) Pyrimidinyl None CH₂pyridinyl NH—C(O) Pyrimidinyl Z₁: F (para) CH₂ pyridinyl NH—C(O)Pyrimidinyl Z₁: F (meta) CH₂ pyridinyl NH—C(O) Pyrimidinyl Z₁: F (ortho)CH₂ pyridinyl NH—C(O) Pyrimidinyl Z₁: F (para) Z₂: F (meta) CH₂Pyridinyl NH—C(O) Pyrimidinyl Z₁: Cl (meta) CH₂ Pyridinyl NH—C(O)Pyrimidinyl Z₁: Cl (para) CH₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁: Cl(para) Z₂: Cl (meta) CH₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁: F (para) Z₂:Cl (meta) CH₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁: Cl (para) Z₂: F (meta)CH₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁: CH₃ (para) CH₂ Pyridinyl NH—C(O)Pyrimidinyl Z₁: CH₃ (meta) CH₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁: CH₃(ortho) CH₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CH₃ (para) CH₂Pyridinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CH₃ (meta) CH₂ Pyridinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CH₃ (ortho) CH₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (para) CH₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) CH₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁: CH₂F(para) CH₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁: CH₂F (meta) CH₂ PyridinylNH—C(O) Pyrimidinyl Z₁: CH₂F (ortho) CH₂ Pyridinyl NH—C(O) PyrimidinylZ₁: CHF₂ (para) CH₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁: CHF₂ (meta) CH₂Pyridinyl NH—C(O) Pyrimidinyl Z₁: CHF₂ (ortho) CH₂ Pyridinyl NH—C(O)Pyrimidinyl Z₁: CF₃ (para) CH₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁: CF₃(meta) CH₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁: CF₃ (ortho) CH₂ PyridinylNH—C(O) Pyrimidinyl Z₁: CH₂—CH₂F (para) CH₂ Pyridinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CH₂F (meta) CH₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CH₂F (ortho) CH₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CHF₂ (para)CH₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CHF₂ (meta) CH₂ PyridinylNH—C(O) Pyrimidinyl Z₁: CH₂—CHF₂ (ortho) CH₂ Pyridinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CF₃ (para) CH₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CF₃ (meta) CH₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CF₃ (ortho) CH₂pyridinyl NH—C(O) Pyrazinyl None CH₂ pyridinyl NH—C(O) Pyrazinyl Z₁: F(para) CH₂ pyridinyl NH—C(O) Pyrazinyl Z₁: F (meta) CH₂ pyridinylNH—C(O) Pyrazinyl Z₁: F (ortho) CH₂ pyridinyl NH—C(O) Pyrazinyl Z₁: F(para) Z₂: F (meta) CH₂ Pyridinyl NH—C(O) Pyrazinyl Z₁: Cl (meta) CH₂Pyridinyl NH—C(O) Pyrazinyl Z₁: Cl (para) CH₂ Pyridinyl NH—C(O)Pyrazinyl Z₁: Cl (para) Z₂: Cl (meta) CH₂ Pyridinyl NH—C(O) PyrazinylZ₁: F (para) Z₂: Cl (meta) CH₂ Pyridinyl NH—C(O) Pyrazinyl Z₁: Cl (para)Z₂: F (meta) CH₂ Pyridinyl NH—C(O) Pyrazinyl Z₁: CH₃ (para) CH₂Pyridinyl NH—C(O) Pyrazinyl Z₁: CH₃ (meta) CH₂ Pyridinyl NH—C(O)Pyrazinyl Z₁: CH₃ (ortho) CH₂ Pyridinyl NH—C(O) Pyrazinyl Z₁: CH₂—CH₃(para) CH₂ Pyridinyl NH—C(O) Pyrazinyl Z₁: CH₂—CH₃ (meta) CH₂ PyridinylNH—C(O) Pyrazinyl Z₁: CH₂—CH₃ (ortho) CH₂ Pyridinyl NH—C(O) PyrazinylZ₁: CH₂—CH₂—CH₃ or iPr (para) CH₂ Pyridinyl NH—C(O) Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) CH₂ Pyridinyl NH—C(O) Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyridinyl NH—C(O) Pyrazinyl Z₁: CH₂F(para) CH₂ Pyridinyl NH—C(O) Pyrazinyl Z₁: CH₂F (meta) CH₂ PyridinylNH—C(O) Pyrazinyl Z₁: CH₂F (ortho) CH₂ Pyridinyl NH—C(O) Pyrazinyl Z₁:CHF₂ (para) CH₂ Pyridinyl NH—C(O) Pyrazinyl Z₁: CHF₂ (meta) CH₂Pyridinyl NH—C(O) Pyrazinyl Z₁: CHF₂ (ortho) CH₂ Pyridinyl NH—C(O)Pyrazinyl Z₁: CF₃ (para) CH₂ Pyridinyl NH—C(O) Pyrazinyl Z₁: CF₃ (meta)CH₂ Pyridinyl NH—C(O) Pyrazinyl Z₁: CF₃ (ortho) CH₂ Pyridinyl NH—C(O)Pyrazinyl Z₁: CH₂—CH₂F (para) CH₂ Pyridinyl NH—C(O) Pyrazinyl Z₁:CH₂—CH₂F (meta) CH₂ Pyridinyl NH—C(O) Pyrazinyl Z₁: CH₂—CH₂F (ortho) CH₂Pyridinyl NH—C(O) Pyrazinyl Z₁: CH₂—CHF₂ (para) CH₂ Pyridinyl NH—C(O)Pyrazinyl Z₁: CH₂—CHF₂ (meta) CH₂ Pyridinyl NH—C(O) Pyrazinyl Z₁:CH₂—CHF₂ (ortho) CH₂ Pyridinyl NH—C(O) Pyrazinyl Z₁: CH₂—CF₃ (para) CH₂Pyridinyl NH—C(O) Pyrazinyl Z₁: CH₂—CF₃ (meta) CH₂ Pyridinyl NH—C(O)Pyrazinyl Z₁: CH₂—CF₃ (ortho) CH₂ pyridinyl NH—C(O) Pyrrolyl None CH₂pyridinyl NH—C(O) Pyrrolyl Z₁: F (2) CH₂ pyridinyl NH—C(O) Pyrrolyl Z₁:F (3) CH₂ pyridinyl NH—C(O) Pyrrolyl Z₁: F (2) Z₂: F (3) CH₂ PyridinylNH—C(O) Pyrrolyl Z₁: Cl (2) CH₂ Pyridinyl NH—C(O) Pyrrolyl Z₁: Cl (3)CH₂ Pyridinyl NH—C(O) Pyrrolyl Z₁: Cl (2) Z₂: Cl (3) CH₂ PyridinylNH—C(O) Pyrrolyl Z₁: F (2) Z₂: Cl (3) CH₂ Pyridinyl NH—C(O) Pyrrolyl Z₁:Cl (2) Z₂: F (3) CH₂ Pyridinyl NH—C(O) Pyrrolyl Z₁: CH₃ (2) CH₂Pyridinyl NH—C(O) Pyrrolyl Z₁: CH₃ (3) CH₂ Pyridinyl NH—C(O) PyrrolylZ₁: CH₂—CH₃ (2) CH₂ Pyridinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₃ (3) CH₂Pyridinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂ PyridinylNH—C(O) Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CH₂ Pyridinyl NH—C(O)Pyrrolyl Z₁: CH₂F (2) CH₂ Pyridinyl NH—C(O) Pyrrolyl Z₁: CH₂F (3) CH₂Pyridinyl NH—C(O) Pyrrolyl Z₁: CHF₂ (2) CH₂ Pyridinyl NH—C(O) PyrrolylZ₁: CHF₂ (3) CH₂ Pyridinyl NH—C(O) Pyrrolyl Z₁: CF₃ (2) CH₂ PyridinylNH—C(O) Pyrrolyl Z₁: CF₃ (3) CH₂ Pyridinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₂F(2) CH₂ Pyridinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₂F (3) CH₂ PyridinylNH—C(O) Pyrrolyl Z₁: CH₂—CHF₂ (2) CH₂ Pyridinyl NH—C(O) Pyrrolyl Z₁:CH₂—CHF₂ (3) CH₂ Pyridinyl NH—C(O) Pyrrolyl Z₁: CH₂—CF₃ (2) CH₂Pyridinyl NH—C(O) Pyrrolyl Z₁: CH₂—CF₃ (3) CH₂ pyridinyl NH—C(O)Imidazolyl None CH₂ pyridinyl NH—C(O) Imidazolyl Z₁: F (2) CH₂ pyridinylNH—C(O) Imidazolyl Z₁: F (3) CH₂ pyridinyl NH—C(O) Imidazolyl Z₁: F (2)Z₂: F (3) CH₂ Pyridinyl NH—C(O) Imidazolyl Z₁: Cl (2) CH₂ PyridinylNH—C(O) Imidazolyl Z₁: Cl (3) CH₂ Pyridinyl NH—C(O) Imidazolyl Z₁: Cl(2) Z₂: Cl (3) CH₂ Pyridinyl NH—C(O) Imidazolyl Z₁: F (2) Z₂: Cl (3) CH₂Pyridinyl NH—C(O) Imidazolyl Z₁: Cl (2) Z₂: F (3) CH₂ Pyridinyl NH—C(O)Imidazolyl Z₁: CH₃ (2) CH₂ Pyridinyl NH—C(O) Imidazolyl Z₁: CH₃ (3) CH₂Pyridinyl NH—C(O) Imidazolyl Z₁: CH₂—CH₃ (2) CH₂ Pyridinyl NH—C(O)Imidazolyl Z₁: CH₂—CH₃ (3) CH₂ Pyridinyl NH—C(O) Imidazolyl Z₁:CH₂—CH₂—CH₃ or iPr (2) CH₂ Pyridinyl NH—C(O) Imidazolyl Z₁: CH₂—CH₂—CH₃or iPr (3) CH₂ Pyridinyl NH—C(O) Imidazolyl Z₁: CH₂F (2) CH₂ PyridinylNH—C(O) Imidazolyl Z₁: CH₂F (3) CH₂ Pyridinyl NH—C(O) Imidazolyl Z₁:CHF₂ (2) CH₂ Pyridinyl NH—C(O) Imidazolyl Z₁: CHF₂ (3) CH₂ PyridinylNH—C(O) Imidazolyl Z₁: CF₃ (2) CH₂ Pyridinyl NH—C(O) Imidazolyl Z₁: CF₃(3) CH₂ Pyridinyl NH—C(O) Imidazolyl Z₁: CH₂—CH₂F (2) CH₂ PyridinylNH—C(O) Imidazolyl Z₁: CH₂—CH₂F (3) CH₂ Pyridinyl NH—C(O) Imidazolyl Z₁:CH₂—CHF₂ (2) CH₂ Pyridinyl NH—C(O) Imidazolyl Z₁: CH₂—CHF₂ (3) CH₂Pyridinyl NH—C(O) Imidazolyl Z₁: CH₂—CF₃ (2) CH₂ Pyridinyl NH—C(O)Imidazolyl Z₁: CH₂—CF₃ (3) CH₂ pyridinyl NH—C(O) Furanyl None CH₂pyridinyl NH—C(O) Furanyl Z₁: F (2) CH₂ pyridinyl NH—C(O) Furanyl Z₁: F(3) CH₂ pyridinyl NH—C(O) Furanyl Z₁: F (2) Z₂: F (3) CH₂ PyridinylNH—C(O) Furanyl Z₁: Cl (2) CH₂ Pyridinyl NH—C(O) Furanyl Z₁: Cl (3) CH₂Pyridinyl NH—C(O) Furanyl Z₁: Cl (2) Z₂: Cl (3) CH₂ Pyridinyl NH—C(O)Furanyl Z₁: F (2) Z₂: Cl (3) CH₂ Pyridinyl NH—C(O) Furanyl Z₁: Cl (2)Z₂: F (3) CH₂ Pyridinyl NH—C(O) Furanyl Z₁: CH₃ (2) CH₂ PyridinylNH—C(O) Furanyl Z₁: CH₃ (3) CH₂ Pyridinyl NH—C(O) Furanyl Z₁: CH₂—CH₃(2) CH₂ Pyridinyl NH—C(O) Furanyl Z₁: CH₂—CH₃ (3) CH₂ Pyridinyl NH—C(O)Furanyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂ Pyridinyl NH—C(O) Furanyl Z₁:CH₂—CH₂—CH₃ or iPr (3) CH₂ Pyridinyl NH—C(O) Furanyl Z₁: CH₂F (2) CH₂Pyridinyl NH—C(O) Furanyl Z₁: CH₂F (3) CH₂ Pyridinyl NH—C(O) Furanyl Z₁:CHF₂ (2) CH₂ Pyridinyl NH—C(O) Furanyl Z₁: CHF₂ (3) CH₂ PyridinylNH—C(O) Furanyl Z₁: CF₃ (2) CH₂ Pyridinyl NH—C(O) Furanyl Z₁: CF₃ (3)CH₂ Pyridinyl NH—C(O) Furanyl Z₁: CH₂—CH₂F (2) CH₂ Pyridinyl NH—C(O)Furanyl Z₁: CH₂—CH₂F (3) CH₂ Pyridinyl NH—C(O) Furanyl Z₁: CH₂—CHF₂ (2)CH₂ Pyridinyl NH—C(O) Furanyl Z₁: CH₂—CHF₂ (3) CH₂ Pyridinyl NH—C(O)Furanyl Z₁: CH₂—CF₃ (2) CH₂ Pyridinyl NH—C(O) Furanyl Z₁: CH₂—CF₃ (3)CH₂ pyridinyl NH—C(O) Oxazolyl None CH₂ pyridinyl NH—C(O) Oxazolyl Z₁: F(2) CH₂ pyridinyl NH—C(O) Oxazolyl Z₁: F (3) CH₂ pyridinyl NH—C(O)Oxazolyl Z₁: F (2) Z₂: F (3) CH₂ Pyridinyl NH—C(O) Oxazolyl Z₁: Cl (2)CH₂ Pyridinyl NH—C(O) Oxazolyl Z₁: Cl (3) CH₂ Pyridinyl NH—C(O) OxazolylZ₁: Cl (2) Z₂: Cl (3) CH₂ Pyridinyl NH—C(O) Oxazolyl Z₁: F (2) Z₂: Cl(3) CH₂ Pyridinyl NH—C(O) Oxazolyl Z₁: Cl (2) Z₂: F (3) CH₂ PyridinylNH—C(O) Oxazolyl Z₁: CH₃ (2) CH₂ Pyridinyl NH—C(O) Oxazolyl Z₁: CH₃ (3)CH₂ Pyridinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₃ (2) CH₂ Pyridinyl NH—C(O)Oxazolyl Z₁: CH₂—CH₃ (3) CH₂ Pyridinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₂—CH₃or iPr (2) CH₂ Pyridinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CH₂Pyridinyl NH—C(O) Oxazolyl Z₁: CH₂F (2) CH₂ Pyridinyl NH—C(O) OxazolylZ₁: CH₂F (3) CH₂ Pyridinyl NH—C(O) Oxazolyl Z₁: CHF₂ (2) CH₂ PyridinylNH—C(O) Oxazolyl Z₁: CHF₂ (3) CH₂ Pyridinyl NH—C(O) Oxazolyl Z₁: CF₃ (2)CH₂ Pyridinyl NH—C(O) Oxazolyl Z₁: CF₃ (3) CH₂ Pyridinyl NH—C(O)Oxazolyl Z₁: CH₂—CH₂F (2) CH₂ Pyridinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₂F(3) CH₂ Pyridinyl NH—C(O) Oxazolyl Z₁: CH₂—CHF₂ (2) CH₂ PyridinylNH—C(O) Oxazolyl Z₁: CH₂—CHF₂ (3) CH₂ Pyridinyl NH—C(O) Oxazolyl Z₁:CH₂—CF₃ (2) CH₂ Pyridinyl NH—C(O) Oxazolyl Z₁: CH₂—CF₃ (3) CH₂ pyridinylNH—C(O) Thiophenyl None CH₂ pyridinyl NH—C(O) Thiophenyl Z₁: F (2) CH₂pyridinyl NH—C(O) Thiophenyl Z₁: F (3) CH₂ pyridinyl NH—C(O) ThiophenylZ₁: F (2) Z₂: F (3) CH₂ Pyridinyl NH—C(O) Thiophenyl Z₁: Cl (2) CH₂Pyridinyl NH—C(O) Thiophenyl Z₁: Cl (3) CH₂ Pyridinyl NH—C(O) ThiophenylZ₁: Cl (2) Z₂: Cl (3) CH₂ Pyridinyl NH—C(O) Thiophenyl Z₁: F (2) Z₂: Cl(3) CH₂ Pyridinyl NH—C(O) Thiophenyl Z₁: Cl (2) Z₂: F (3) CH₂ PyridinylNH—C(O) Thiophenyl Z₁: CH₃ (2) CH₂ Pyridinyl NH—C(O) Thiophenyl Z₁: CH₃(3) CH₂ Pyridinyl NH—C(O) Thiophenyl Z₁: CH₂—CH₃ (2) CH₂ PyridinylNH—C(O) Thiophenyl Z₁: CH₂—CH₃ (3) CH₂ Pyridinyl NH—C(O) Thiophenyl Z₁:CH₂—CH₂—CH₃ or iPr (2) CH₂ Pyridinyl NH—C(O) Thiophenyl Z₁: CH₂—CH₂—CH₃or iPr (3) CH₂ Pyridinyl NH—C(O) Thiophenyl Z₁: CH₂F (2) CH₂ PyridinylNH—C(O) Thiophenyl Z₁: CH₂F (3) CH₂ Pyridinyl NH—C(O) Thiophenyl Z₁:CHF₂ (2) CH₂ Pyridinyl NH—C(O) Thiophenyl Z₁: CHF₂ (3) CH₂ PyridinylNH—C(O) Thiophenyl Z₁: CF₃ (2) CH₂ Pyridinyl NH—C(O) Thiophenyl Z₁: CF₃(3) CH₂ Pyridinyl NH—C(O) Thiophenyl Z₁: CH₂—CH₂F (2) CH₂ PyridinylNH—C(O) Thiophenyl Z₁: CH₂—CH₂F (3) CH₂ Pyridinyl NH—C(O) Thiophenyl Z₁:CH₂—CHF₂ (2) CH₂ Pyridinyl NH—C(O) Thiophenyl Z₁: CH₂—CHF₂ (3) CH₂Pyridinyl NH—C(O) Thiophenyl Z₁: CH₂—CF₃ (2) CH₂ Pyridinyl NH—C(O)Thiophenyl Z₁: CH₂—CF₃ (3) CH₂ pyridinyl NH—C(O) Thiazolyl None CH₂pyridinyl NH—C(O) Thiazolyl Z₁: F (2) CH₂ pyridinyl NH—C(O) ThiazolylZ₁: F (3) CH₂ pyridinyl NH—C(O) Thiazolyl Z₁: F (2) Z₂: F (3) CH₂Pyridinyl NH—C(O) Thiazolyl Z₁: Cl (2) CH₂ Pyridinyl NH—C(O) ThiazolylZ₁: Cl (3) CH₂ Pyridinyl NH—C(O) Thiazolyl Z₁: Cl (2) Z₂: Cl (3) CH₂Pyridinyl NH—C(O) Thiazolyl Z₁: F (2) Z₂: Cl (3) CH₂ Pyridinyl NH—C(O)Thiazolyl Z₁: Cl (2) Z₂: F (3) CH₂ Pyridinyl NH—C(O) Thiazolyl Z₁: CH₃(2) CH₂ Pyridinyl NH—C(O) Thiazolyl Z₁: CH₃ (3) CH₂ Pyridinyl NH—C(O)Thiazolyl Z₁: CH₂—CH₃ (2) CH₂ Pyridinyl NH—C(O) Thiazolyl Z₁: CH₂—CH₃(3) CH₂ Pyridinyl NH—C(O) Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂Pyridinyl NH—C(O) Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CH₂ PyridinylNH—C(O) Thiazolyl Z₁: CH₂F (2) CH₂ Pyridinyl NH—C(O) Thiazolyl Z₁: CH₂F(3) CH₂ Pyridinyl NH—C(O) Thiazolyl Z₁: CHF₂ (2) CH₂ Pyridinyl NH—C(O)Thiazolyl Z₁: CHF₂ (3) CH₂ Pyridinyl NH—C(O) Thiazolyl Z₁: CF₃ (2) CH₂Pyridinyl NH—C(O) Thiazolyl Z₁: CF₃ (3) CH₂ Pyridinyl NH—C(O) ThiazolylZ₁: CH₂—CH₂F (2) CH₂ Pyridinyl NH—C(O) Thiazolyl Z₁: CH₂—CH₂F (3) CH₂Pyridinyl NH—C(O) Thiazolyl Z₁: CH₂—CHF₂ (2) CH₂ Pyridinyl NH—C(O)Thiazolyl Z₁: CH₂—CHF₂ (3) CH₂ Pyridinyl NH—C(O) Thiazolyl Z₁: CH₂—CF₃(2) CH₂ Pyridinyl NH—C(O) Thiazolyl Z₁: CH₂—CF₃ (3) CH₂ pyridinyl NH—SO₂Phenyl None CH₂ pyridinyl NH—SO₂ Phenyl Z₁: F (para) CH₂ pyridinylNH—SO₂ phenyl Z₁: F (meta) CH₂ pyridinyl NH—SO₂ phenyl Z₁: F (ortho) CH₂pyridinyl NH—SO₂ phenyl Z₁: F (para) Z₂: F (meta) CH₂ Pyridinyl NH—SO₂Phenyl Z₁: Cl (meta) CH₂ Pyridinyl NH—SO₂ Phenyl Z₁: Cl (para) CH₂Pyridinyl NH—SO₂ Phenyl Z₁: Cl (para) Z₂: Cl (meta) CH₂ Pyridinyl NH—SO₂Phenyl Z₁: F (para) Z₂: Cl (meta) CH₂ Pyridinyl NH—SO₂ Phenyl Z₁: Cl(para) Z₂: F (meta) CH₂ Pyridinyl NH—SO₂ Phenyl Z₁: CH₃ (para) CH₂Pyridinyl NH—SO₂ Phenyl Z₁: CH₃ (meta) CH₂ Pyridinyl NH—SO₂ Phenyl Z₁:CH₃ (ortho) CH₂ Pyridinyl NH—SO₂ Phenyl Z₁: CH₂—CH₃ (para) CH₂ PyridinylNH—SO₂ Phenyl Z₁: CH₂—CH₃ (meta) CH₂ Pyridinyl NH—SO₂ Phenyl Z₁: CH₂—CH₃(ortho) CH₂ Pyridinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CH₂Pyridinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CH₂ PyridinylNH—SO₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyridinyl NH—SO₂ PhenylZ₁: CH₂F (para) CH₂ Pyridinyl NH—SO₂ Phenyl Z₁: CH₂F (meta) CH₂Pyridinyl NH—SO₂ Phenyl Z₁: CH₂F (ortho) CH₂ Pyridinyl NH—SO₂ Phenyl Z₁:CHF₂ (para) CH₂ Pyridinyl NH—SO₂ Phenyl Z₁: CHF₂ (meta) CH₂ PyridinylNH—SO₂ Phenyl Z₁: CHF₂ (ortho) CH₂ Pyridinyl NH—SO₂ Phenyl Z₁: CF₃(para) CH₂ Pyridinyl NH—SO₂ Phenyl Z₁: CF₃ (meta) CH₂ Pyridinyl NH—SO₂Phenyl Z₁: CF₃ (ortho) CH₂ Pyridinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂F (para)CH₂ Pyridinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂F (meta) CH₂ Pyridinyl NH—SO₂Phenyl Z₁: CH₂—CH₂F (ortho) CH₂ Pyridinyl NH—SO₂ Phenyl Z₁: CH₂—CHF₂(para) CH₂ Pyridinyl NH—SO₂ Phenyl Z₁: CH₂—CHF₂ (meta) CH₂ PyridinylNH—SO₂ Phenyl Z₁: CH₂—CHF₂ (ortho) CH₂ Pyridinyl NH—SO₂ Phenyl Z₁:CH₂—CF₃ (para) CH₂ Pyridinyl NH—SO₂ Phenyl Z₁: CH₂—CF₃ (meta) CH₂Pyridinyl NH—SO₂ Phenyl Z₁: CH₂—CF₃ (ortho) CH₂ pyridinyl NH—SO₂Pyridinyl None CH₂ pyridinyl NH—SO₂ Pyridinyl Z₁: F (para) CH₂ pyridinylNH—SO₂ Pyridinyl Z₁: F (meta) CH₂ pyridinyl NH—SO₂ Pyridinyl Z₁: F(ortho) CH₂ pyridinyl NH—SO₂ Pyridinyl Z₁: F (para) Z₂: F (meta) CH₂Pyridinyl NH—SO₂ Pyridinyl Z₁: Cl (meta) CH₂ Pyridinyl NH—SO₂ PyridinylZ₁: Cl (para) CH₂ Pyridinyl NH—SO₂ Pyridinyl Z₁: Cl (para) Z₂: Cl (meta)CH₂ Pyridinyl NH—SO₂ Pyridinyl Z₁: F (para) Z₂: Cl (meta) CH₂ PyridinylNH—SO₂ Pyridinyl Z₁: Cl (para) Z₂: F (meta) CH₂ Pyridinyl NH—SO₂Pyridinyl Z₁: CH₃ (para) CH₂ Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₃ (meta)CH₂ Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₃ (ortho) CH₂ Pyridinyl NH—SO₂Pyridinyl Z₁: CH₂—CH₂ (para) CH₂ Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₃(meta) CH₂ Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₃ (ortho) CH₂ PyridinylNH—SO₂ Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CH₂ Pyridinyl NH—SO₂Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CH₂ Pyridinyl NH—SO₂ PyridinylZ₁: CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₂F(para) CH₂ Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₂F (meta) CH₂ PyridinylNH—SO₂ Pyridinyl Z₁: CH₂F (ortho) CH₂ Pyridinyl NH—SO₂ Pyridinyl Z₁:CHF₂ (para) CH₂ Pyridinyl NH—SO₂ Pyridinyl Z₁: CHF₂ (meta) CH₂ PyridinylNH—SO₂ Pyridinyl Z₁: CHF₂ (ortho) CH₂ Pyridinyl NH—SO₂ Pyridinyl Z₁: CF₃(para) CH₂ Pyridinyl NH—SO₂ Pyridinyl Z₁: CF₃ (meta) CH₂ PyridinylNH—SO₂ Pyridinyl Z₁: CF₃ (ortho) CH₂ Pyridinyl NH—SO₂ Pyridinyl Z₁:CH₂—CH₂F (para) CH₂ Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₂F (meta) CH₂Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₂F (ortho) CH₂ Pyridinyl NH—SO₂Pyridinyl Z₁: CH₂—CHF₂ (para) CH₂ Pyridinyl NH—SO₂ Pyridinyl Z₁:CH₂—CHF₂ (meta) CH₂ Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₂—CHF₂ (ortho) CH₂Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₂—CF₃ (para) CH₂ Pyridinyl NH—SO₂Pyridinyl Z₁: CH₂—CF₃ (meta) CH₂ Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₂—CF₃(ortho) CH₂ pyridinyl NH—SO₂ Pyrimidinyl None CH₂ pyridinyl NH—SO₂Pyrimidinyl Z₁: F (para) CH₂ pyridinyl NH—SO₂ Pyrimidinyl Z₁: F (meta)CH₂ pyridinyl NH—SO₂ Pyrimidinyl Z₁: F (ortho) CH₂ pyridinyl NH—SO₂Pyrimidinyl Z₁: F (para) Z₂: F (meta) CH₂ Pyridinyl NH—SO₂ PyrimidinylZ₁: Cl (meta) CH₂ Pyridinyl NH—SO₂ Pyrimidinyl Z₁: Cl (para) CH₂Pyridinyl NH—SO₂ Pyrimidinyl Z₁: Cl (para) Z₂: Cl (meta) CH₂ PyridinylNH—SO₂ Pyrimidinyl Z₁: F (para) Z₂: Cl (meta) CH₂ Pyridinyl NH—SO₂Pyrimidinyl Z₁: Cl (para) Z₂: F (meta) CH₂ Pyridinyl NH—SO₂ PyrimidinylZ₁: CH₃ (para) CH₂ Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₃ (meta) CH₂Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₃ (ortho) CH₂ Pyridinyl NH—SO₂Pyrimidinyl Z₁: CH₂—CH₃ (para) CH₂ Pyridinyl NH—SO₂ Pyrimidinyl Z₁:CH₂—CH₃ (meta) CH₂ Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₃ (ortho) CH₂Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CH₂ PyridinylNH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CH₂ Pyridinyl NH—SO₂Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyridinyl NH—SO₂Pyrimidinyl Z₁: CH₂F (para) CH₂ Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₂F(meta) CH₂ Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₂F (ortho) CH₂ PyridinylNH—SO₂ Pyrimidinyl Z₁: CHF₂ (para) CH₂ Pyridinyl NH—SO₂ Pyrimidinyl Z₁:CHF₂ (meta) CH₂ Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CHF₂ (ortho) CH₂Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CF₃ (para) CH₂ Pyridinyl NH—SO₂Pyrimidinyl Z₁: CF₃ (meta) CH₂ Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CF₃(ortho) CH₂ Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂F (para) CH₂Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂F (meta) CH₂ Pyridinyl NH—SO₂Pyrimidinyl Z₁: CH₂—CH₂F (ortho) CH₂ Pyridinyl NH—SO₂ Pyrimidinyl Z₁:CH₂—CHF₂ (para) CH₂ Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CHF₂ (meta) CH₂Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CHF₂ (ortho) CH₂ Pyridinyl NH—SO₂Pyrimidinyl Z₁: CH₂—CF₃ (para) CH₂ Pyridinyl NH—SO₂ Pyrimidinyl Z₁:CH₂—CF₃ (meta) CH₂ Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CF₃ (ortho) CH₂pyridinyl NH—SO₂ Pyrazinyl None CH₂ pyridinyl NH—SO₂ Pyrazinyl Z₁: F(para) CH₂ pyridinyl NH—SO₂ Pyrazinyl Z₁: F (meta) CH₂ pyridinyl NH—SO₂Pyrazinyl Z₁: F (ortho) CH₂ pyridinyl NH—SO₂ Pyrazinyl Z₁: F (para) Z₂:F (meta) CH₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: Cl (meta) CH₂ PyridinylNH—SO₂ Pyrazinyl Z₁: Cl (para) CH₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: Cl(para) Z₂: Cl (meta) CH₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: F (para) Z₂: Cl(meta) CH₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: Cl (para) Z₂: F (meta) CH₂Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₃ (para) CH₂ Pyridinyl NH—SO₂ PyrazinylZ₁: CH₃ (meta) CH₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₃ (ortho) CH₂Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₃ (para) CH₂ Pyridinyl NH—SO₂Pyrazinyl Z₁: CH₂—CH₃ (meta) CH₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₃(ortho) CH₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CH₂Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CH₂ PyridinylNH—SO₂ Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyridinyl NH—SO₂Pyrazinyl Z₁: CH₂F (para) CH₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₂F (meta)CH₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₂F (ortho) CH₂ Pyridinyl NH—SO₂Pyrazinyl Z₁: CHF₂ (para) CH₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: CHF₂ (meta)CH₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: CHF₂ (ortho) CH₂ Pyridinyl NH—SO₂Pyrazinyl Z₁: CF₃ (para) CH₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: CF₃ (meta)CH₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: CF₃ (ortho) CH₂ Pyridinyl NH—SO₂Pyrazinyl Z₁: CH₂—CH₂F (para) CH₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁:CH₂—CH₂F (meta) CH₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₂F (ortho) CH₂Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CHF₂ (para) CH₂ Pyridinyl NH—SO₂Pyrazinyl Z₁: CH₂—CHF₂ (meta) CH₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁:CH₂—CHF₂ (ortho) CH₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CF₃ (para) CH₂Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CF₃ (meta) CH₂ Pyridinyl NH—SO₂Pyrazinyl Z₁: CH₂—CF₃ (ortho) CH₂ pyridinyl NH—SO₂ Pyrrolyl None CH₂pyridinyl NH—SO₂ Pyrrolyl Z₁: F (2) CH₂ pyridinyl NH—SO₂ Pyrrolyl Z₁: F(3) CH₂ pyridinyl NH—SO₂ Pyrrolyl Z₁: F (2) Z₂: F (3) CH₂ PyridinylNH—SO₂ Pyrrolyl Z₁: Cl (2) CH₂ Pyridinyl NH—SO₂ Pyrrolyl Z₁: Cl (3) CH₂Pyridinyl NH—SO₂ Pyrrolyl Z₁: Cl (2) Z₂: Cl (3) CH₂ Pyridinyl NH—SO₂Pyrrolyl Z₁: F (2) Z₂: Cl (3) CH₂ Pyridinyl NH—SO₂ Pyrrolyl Z₁: Cl (2)Z₂: F (3) CH₂ Pyridinyl NH—SO₂ Pyrrolyl Z₁: CH₃ (2) CH₂ Pyridinyl NH—SO₂Pyrrolyl Z₁: CH₃ (3) CH₂ Pyridinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CH₃ (2) CH₂Pyridinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CH₃ (3) CH₂ Pyridinyl NH—SO₂ PyrrolylZ₁: CH₂—CH₂—CH₃ or iPr (2) CH₂ Pyridinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CH₂—CH₃or iPr (3) CH₂ Pyridinyl NH—SO₂ Pyrrolyl Z₁: CH₂F (2) CH₂ PyridinylNH—SO₂ Pyrrolyl Z₁: CH₂F (3) CH₂ Pyridinyl NH—SO₂ Pyrrolyl Z₁: CHF₂ (2)CH₂ Pyridinyl NH—SO₂ Pyrrolyl Z₁: CHF₂ (3) CH₂ Pyridinyl NH—SO₂ PyrrolylZ₁: CF₃ (2) CH₂ Pyridinyl NH—SO₂ Pyrrolyl Z₁: CF₃ (3) CH₂ PyridinylNH—SO₂ Pyrrolyl Z₁: CH₂—CH₂F (2) CH₂ Pyridinyl NH—SO₂ Pyrrolyl Z₁:CH₂—CH₂F (3) CH₂ Pyridinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CHF₂ (2) CH₂Pyridinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CHF₂ (3) CH₂ Pyridinyl NH—SO₂ PyrrolylZ₁: CH₂—CF₃ (2) CH₂ Pyridinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CF₃ (3) CH₂pyridinyl NH—SO₂ Imidazolyl None CH₂ pyridinyl NH—SO₂ Imidazolyl Z₁: F(2) CH₂ pyridinyl NH—SO₂ Imidazolyl Z₁: F (3) CH₂ pyridinyl NH—SO₂Imidazolyl Z₁: F (2) Z₂: F (3) CH₂ Pyridinyl NH—SO₂ Imidazolyl Z₁: Cl(2) CH₂ Pyridinyl NH—SO₂ Imidazolyl Z₁: Cl (3) CH₂ Pyridinyl NH—SO₂Imidazolyl Z₁: Cl (2) Z₂: Cl (3) CH₂ Pyridinyl NH—SO₂ Imidazolyl Z₁: F(2) Z₂: Cl (3) CH₂ Pyridinyl NH—SO₂ Imidazolyl Z₁: Cl (2) Z₂: F (3) CH₂Pyridinyl NH—SO₂ Imidazolyl Z₁: CH₃ (2) CH₂ Pyridinyl NH—SO₂ ImidazolylZ₁: CH₃ (3) CH₂ Pyridinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₃ (2) CH₂Pyridinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₃ (3) CH₂ Pyridinyl NH—SO₂Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂ Pyridinyl NH—SO₂ ImidazolylZ₁: CH₂—CH₂—CH₃ or iPr (3) CH₂ Pyridinyl NH—SO₂ Imidazolyl Z₁: CH₂F (2)CH₂ Pyridinyl NH—SO₂ Imidazolyl Z₁: CH₂F (3) CH₂ Pyridinyl NH—SO₂Imidazolyl Z₁: CHF₂ (2) CH₂ Pyridinyl NH—SO₂ Imidazolyl Z₁: CHF₂ (3) CH₂Pyridinyl NH—SO₂ Imidazolyl Z₁: CF₃ (2) CH₂ Pyridinyl NH—SO₂ ImidazolylZ₁: CF₃ (3) CH₂ Pyridinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₂F (2) CH₂Pyridinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₂F (3) CH₂ Pyridinyl NH—SO₂Imidazolyl Z₁: CH₂—CHF₂ (2) CH₂ Pyridinyl NH—SO₂ Imidazolyl Z₁: CH₂—CHF₂(3) CH₂ Pyridinyl NH—SO₂ Imidazolyl Z₁: CH₂—CF₃ (2) CH₂ Pyridinyl NH—SO₂Imidazolyl Z₁: CH₂—CF₃ (3) CH₂ pyridinyl NH—SO₂ Furanyl None CH₂pyridinyl NH—SO₂ Furanyl Z₁: F (2) CH₂ pyridinyl NH—SO₂ Furanyl Z₁: F(3) CH₂ pyridinyl NH—SO₂ Furanyl Z₁: F (2) Z₂: F (3) CH₂ PyridinylNH—SO₂ Furanyl Z₁: Cl (2) CH₂ Pyridinyl NH—SO₂ Furanyl Z₁: Cl (3) CH₂Pyridinyl NH—SO₂ Furanyl Z₁: Cl (2) Z₂: Cl (3) CH₂ Pyridinyl NH—SO₂Furanyl Z₁: F (2) Z₂: Cl (3) CH₂ Pyridinyl NH—SO₂ Furanyl Z₁: Cl (2) Z₂:F (3) CH₂ Pyridinyl NH—SO₂ Furanyl Z₁: CH₃ (2) CH₂ Pyridinyl NH—SO₂Furanyl Z₁: CH₃ (3) CH₂ Pyridinyl NH—SO₂ Furanyl Z₁: CH₂—CH₃ (2) CH₂Pyridinyl NH—SO₂ Furanyl Z₁: CH₂—CH₃ (3) CH₂ Pyridinyl NH—SO₂ FuranylZ₁: CH₂—CH₂—CH₃ or iPr (2) CH₂ Pyridinyl NH—SO₂ Furanyl Z₁: CH₂—CH₂—CH₃or iPr (3) CH₂ Pyridinyl NH—SO₂ Furanyl Z₁: CH₂F (2) CH₂ PyridinylNH—SO₂ Furanyl Z₁: CH₂F (3) CH₂ Pyridinyl NH—SO₂ Furanyl Z₁: CHF₂ (2)CH₂ Pyridinyl NH—SO₂ Furanyl Z₁: CHF₂ (3) CH₂ Pyridinyl NH—SO₂ FuranylZ₁: CF₃ (2) CH₂ Pyridinyl NH—SO₂ Furanyl Z₁: CF₃ (3) CH₂ PyridinylNH—SO₂ Furanyl Z₁: CH₂—CH₂F (2) CH₂ Pyridinyl NH—SO₂ Furanyl Z₁:CH₂—CH₂F (3) CH₂ Pyridinyl NH—SO₂ Furanyl Z₁: CH₂—CHF₂ (2) CH₂ PyridinylNH—SO₂ Furanyl Z₁: CH₂—CHF₂ (3) CH₂ Pyridinyl NH—SO₂ Furanyl Z₁: CH₂—CF₃(2) CH₂ Pyridinyl NH—SO₂ Furanyl Z₁: CH₂—CF₃ (3) CH₂ pyridinyl NH—SO₂Oxazolyl None CH₂ pyridinyl NH—SO₂ Oxazolyl Z₁: F (2) CH₂ pyridinylNH—SO₂ Oxazolyl Z₁: F (3) CH₂ pyridinyl NH—SO₂ Oxazolyl Z₁: F (2) Z₁: F(3) CH₂ Pyridinyl NH—SO₂ Oxazolyl Z₁: Cl (2) CH₂ Pyridinyl NH—SO₂Oxazolyl Z₁: Cl (3) CH₂ Pyridinyl NH—SO₂ Oxazolyl Z₁: Cl (2) Z₂: Cl (3)CH₂ Pyridinyl NH—SO₂ Oxazolyl Z₁: F (2) Z₂: Cl (3) CH₂ Pyridinyl NH—SO₂Oxazolyl Z₁: Cl (2) Z₂: F (3) CH₂ Pyridinyl NH—SO₂ Oxazolyl Z₁: CH₃ (2)CH₂ Pyridinyl NH—SO₂ Oxazolyl Z₁: CH₃ (3) CH₂ Pyridinyl NH—SO₂ OxazolylZ₁: CH₂—CH₃ (2) CH₂ Pyridinyl NH—SO₂ Oxazolyl Z₁: CH₂—CH₃ (3) CH₂Pyridinyl NH—SO₂ Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂ PyridinylNH—SO₂ Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CH₂ Pyridinyl NH—SO₂ OxazolylZ₁: CH₂F (2) CH₂ Pyridinyl NH—SO₂ Oxazolyl Z₁: CH₂F (3) CH₂ PyridinylNH—SO₂ Oxazolyl Z₁: CHF₂ (2) CH₂ Pyridinyl NH—SO₂ Oxazolyl Z₁: CHF₂ (3)CH₂ Pyridinyl NH—SO₂ Oxazolyl Z₁: CF₃ (2) CH₂ Pyridinyl NH—SO₂ OxazolylZ₁: CF₃ (3) CH₂ Pyridinyl NH—SO₂ Oxazolyl Z₁: CH₂—CH₂F (2) CH₂ PyridinylNH—SO₂ Oxazolyl Z₁: CH₂—CH₂F (3) CH₂ Pyridinyl NH—SO₂ Oxazolyl Z₁:CH₂—CHF₂ (2) CH₂ Pyridinyl NH—SO₂ Oxazolyl Z₁: CH₂—CHF₂ (3) CH₂Pyridinyl NH—SO₂ Oxazolyl Z₁: CH₂—CF₃ (2) CH₂ Pyridinyl NH—SO₂ OxazolylZ₁: CH₂—CF₃ (3) CH₂ pyridinyl NH—SO₂ Thiophenyl None CH₂ pyridinylNH—SO₂ Thiophenyl Z₁: F (2) CH₂ pyridinyl NH—SO₂ Thiophenyl Z₁: F (3)CH₂ pyridinyl NH—SO₂ Thiophenyl Z₁: F (2) Z₂: F (3) CH₂ Pyridinyl NH—SO₂Thiophenyl Z₁: Cl (2) CH₂ Pyridinyl NH—SO₂ Thiophenyl Z₁: Cl (3) CH₂Pyridinyl NH—SO₂ Thiophenyl Z₁: Cl (2) Z₂: Cl (3) CH₂ Pyridinyl NH—SO₂Thiophenyl Z₁: F (2) Z₂: Cl (3) CH₂ Pyridinyl NH—SO₂ Thiophenyl Z₁: Cl(2) Z₂: F (3) CH₂ Pyridinyl NH—SO₂ Thiophenyl Z₁: CH₃ (2) CH₂ PyridinylNH—SO₂ Thiophenyl Z₁: CH₃ (3) CH₂ Pyridinyl NH—SO₂ Thiophenyl Z₁:CH₂—CH₃ (2) CH₂ Pyridinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₃ (3) CH₂Pyridinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂ PyridinylNH—SO₂ Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CH₂ Pyridinyl NH—SO₂Thiophenyl Z₁: CH₂F (2) CH₂ Pyridinyl NH—SO₂ Thiophenyl Z₁: CH₂F (3) CH₂Pyridinyl NH—SO₂ Thiophenyl Z₁: CHF₂ (2) CH₂ Pyridinyl NH—SO₂ ThiophenylZ₁: CHF₂ (3) CH₂ Pyridinyl NH—SO₂ Thiophenyl Z₁: CF₃ (2) CH₂ PyridinylNH—SO₂ Thiophenyl Z₁: CF₃ (3) CH₂ Pyridinyl NH—SO₂ Thiophenyl Z₁:CH₂—CH₂F (2) CH₂ Pyridinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₂F (3) CH₂Pyridinyl NH—SO₂ Thiophenyl Z₁: CH₂—CHF₂ (2) CH₂ Pyridinyl NH—SO₂Thiophenyl Z₁: CH₂—CHF₂ (3) CH₂ Pyridinyl NH—SO₂ Thiophenyl Z₁: CH₂—CF₃(2) CH₂ Pyridinyl NH—SO₂ Thiophenyl Z₁: CH₂—CF₃ (3) CH₂ pyridinyl NH—SO₂Thiazolyl None CH₂ pyridinyl NH—SO₂ Thiazolyl Z₁: F (2) CH₂ pyridinylNH—SO₂ Thiazolyl Z₁: F (3) CH₂ pyridinyl NH—SO₂ Thiazolyl Z₁: F (2) Z₂:F (3) CH₂ Pyridinyl NH—SO₂ Thiazolyl Z₁: Cl (2) CH₂ Pyridinyl NH—SO₂Thiazolyl Z₁: Cl (3) CH₂ Pyridinyl NH—SO₂ Thiazolyl Z₁: Cl (2) Z₂: Cl(3) CH₂ Pyridinyl NH—SO₂ Thiazolyl Z₁: F (2) Z₂: Cl (3) CH₂ PyridinylNH—SO₂ Thiazolyl Z₁: Cl (2) Z₂: F (3) CH₂ Pyridinyl NH—SO₂ Thiazolyl Z₁:CH₃ (2) CH₂ Pyridinyl NH—SO₂ Thiazolyl Z₁: CH₃ (3) CH₂ Pyridinyl NH—SO₂Thiazolyl Z₁: CH₂—CH₃ (2) CH₂ Pyridinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₃ (3)CH₂ Pyridinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂ PyridinylNH—SO₂ Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CH₂ Pyridinyl NH—SO₂Thiazolyl Z₁: CH₂F (2) CH₂ Pyridinyl NH—SO₂ Thiazolyl Z₁: CH₂F (3) CH₂Pyridinyl NH—SO₂ Thiazolyl Z₁: CHF₂ (2) CH₂ Pyridinyl NH—SO₂ ThiazolylZ₁: CHF₂ (3) CH₂ Pyridinyl NH—SO₂ Thiazolyl Z₁: CF₃ (2) CH₂ PyridinylNH—SO₂ Thiazolyl Z₁: CF₃ (3) CH₂ Pyridinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₂F(2) CH₂ Pyridinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₂F (3) CH₂ Pyridinyl NH—SO₂Thiazolyl Z₁: CH₂—CHF₂ (2) CH₂ Pyridinyl NH—SO₂ Thiazolyl Z₁: CH₂—CHF₂(3) CH₂ Pyridinyl NH—SO₂ Thiazolyl Z₁: CH₂—CF₃ (2) CH₂ Pyridinyl NH—SO₂Thiazolyl Z₁: CH₂—CF₃ (3) CH₂ Pyrimidinyl NH—CH₂ Phenyl None CH₂Pyrimidinyl NH—CH₂ Phenyl Z₁: F (para) CH₂ Pyrimidinyl NH—CH₂ phenyl Z₁:F (meta) CH₂ Pyrimidinyl NH—CH₂ phenyl Z₁: F (ortho) CH₂ PyrimidinylNH—CH₂ phenyl Z₁: F (para) Z₂: F (meta) CH₂ Pyrimidinyl NH—CH₂ PhenylZ₁: Cl (meta) CH₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: Cl (para) CH₂Pyrimidinyl NH—CH₂ Phenyl Z₁: Cl (para) Z₂: Cl (meta) CH₂ PyrimidinylNH—CH₂ Phenyl Z₁: F (para) Z₂: Cl (meta) CH₂ Pyrimidinyl NH—CH₂ PhenylZ₁: Cl (para) Z₂: F (meta) CH₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₃ (para)CH₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₃ (meta) CH₂ Pyrimidinyl NH—CH₂Phenyl Z₁: CH₃ (ortho) CH₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CH₃ (para)CH₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CH₃ (meta) CH₂ Pyrimidinyl NH—CH₂Phenyl Z₁: CH₂—CH₃ (ortho) CH₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂—CH₃or iPr (para) CH₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr(meta) CH₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) CH₂Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂F (para) CH₂ Pyrimidinyl NH—CH₂ PhenylZ₁: CH₂F (meta) CH₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂F (ortho) CH₂Pyrimidinyl NH—CH₂ Phenyl Z₁: CHF₂ (para) CH₂ Pyrimidinyl NH—CH₂ PhenylZ₁: CHF₂ (meta) CH₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: CHF₂ (ortho) CH₂Pyrimidinyl NH—CH₂ Phenyl Z₁: CF₃ (para) CH₂ Pyrimidinyl NH—CH₂ PhenylZ₁: CF₃ (meta) CH₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: CF₃ (ortho) CH₂Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂F (para) CH₂ Pyrimidinyl NH—CH₂Phenyl Z₁: CH₂—CH₂F (meta) CH₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂F(ortho) CH₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CHF₂ (para) CH₂Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CHF₂ (meta) CH₂ Pyrimidinyl NH—CH₂Phenyl Z₁: CH₂—CHF₂ (ortho) CH₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CF₃(para) CH₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CF₃ (meta) CH₂ PyrimidinylNH—CH₂ Phenyl Z₁: CH₂—CF₃ (ortho) CH₂ Pyrimidinyl NH—CH₂ Pyridinyl NoneCH₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: F (para) CH₂ Pyrimidinyl NH—CH₂Pyridinyl Z₁: F (meta) CH₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: F (ortho)CH₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: F (para) Z₂: F (meta) CH₂Pyrimidinyl NH—CH₂ Pyridinyl Z₁: Cl (meta) CH₂ Pyrimidinyl NH—CH₂Pyridinyl Z₁: Cl (para) CH₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: Cl (para)Z₂: Cl (meta) CH₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: F (para) Z₂: Cl(meta) CH₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: Cl (para) Z₂: F (meta) CH₂Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₃ (para) CH₂ Pyrimidinyl NH—CH₂Pyridinyl Z₁: CH₃ (meta) CH₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₃(ortho) CH₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₃ (para) CH₂Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₃ (meta) CH₂ Pyrimidinyl NH—CH₂Pyridinyl Z₁: CH₂—CH₃ (ortho) CH₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁:CH₂—CH₂—CH₃ or iPr (para) CH₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) CH₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₂F(para) CH₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₂F (meta) CH₂ PyrimidinylNH—CH₂ Pyridinyl Z₁: CH₂F (ortho) CH₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁:CHF₂ (para) CH₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CHF₂ (meta) CH₂Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CHF₂ (ortho) CH₂ Pyrimidinyl NH—CH₂Pyridinyl Z₁: CF₃ (para) CH₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CF₃ (meta)CH₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CF₃ (ortho) CH₂ Pyrimidinyl NH—CH₂Pyridinyl Z₁: CH₂—CH₂F (para) CH₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁:CH₂—CH₂F (meta) CH₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₂F (ortho)CH₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₂—CHF₂ (para) CH₂ PyrimidinylNH—CH₂ Pyridinyl Z₁: CH₂—CHF₂ (meta) CH₂ Pyrimidinyl NH—CH₂ PyridinylZ₁: CH₂—CHF₂ (ortho) CH₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₂—CF₃ (para)CH₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₂—CF₃ (meta) CH₂ PyrimidinylNH—CH₂ Pyridinyl Z₁: CH₂—CF₃ (ortho) CH₂ Pyrimidinyl NH—CH₂ PyrimidinylNone CH₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: F (para) CH₂ PyrimidinylNH—CH₂ Pyrimidinyl Z₁: F (meta) CH₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: F(ortho) CH₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: F (para) Z₂: F (meta) CH₂Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: Cl (meta) CH₂ Pyrimidinyl NH—CH₂Pyrimidinyl Z₁: Cl (para) CH₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: Cl(para) Z₂: Cl (meta) CH₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: F (para) Z₂:Cl (meta) CH₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: Cl (para) Z₂: F (meta)CH₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₃ (para) CH₂ Pyrimidinyl NH—CH₂Pyrimidinyl Z₁: CH₃ (meta) CH₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₃(ortho) CH₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₃ (para) CH₂Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₃ (meta) CH₂ Pyrimidinyl NH—CH₂Pyrimidinyl Z₁: CH₂—CH₃ (ortho) CH₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (para) CH₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) CH₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₂F(para) CH₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₂F (meta) CH₂Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₂F (ortho) CH₂ Pyrimidinyl NH—CH₂Pyrimidinyl Z₁: CHF₂ (para) CH₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CHF₂(meta) CH₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CHF₂ (ortho) CH₂Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CF₃ (para) CH₂ Pyrimidinyl NH—CH₂Pyrimidinyl Z₁: CF₃ (meta) CH₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CF₃(ortho) CH₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₂F (para) CH₂Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₂F (meta) CH₂ PyrimidinylNH—CH₂ Pyrimidinyl Z₁: CH₂—CH₂F (ortho) CH₂ Pyrimidinyl NH—CH₂Pyrimidinyl Z₁: CH₂—CHF₂ (para) CH₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁:CH₂—CHF₂ (meta) CH₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CHF₂ (ortho)CH₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CF₃ (para) CH₂ PyrimidinylNH—CH₂ Pyrimidinyl Z₁: CH₂—CF₃ (meta) CH₂ Pyrimidinyl NH—CH₂ PyrimidinylZ₁: CH₂—CF₃ (ortho) CH₂ Pyrimidinyl NH—CH₂ Pyrazinyl None CH₂Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: F (para) CH₂ Pyrimidinyl NH—CH₂Pyrazinyl Z₁: F (meta) CH₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: F (ortho)CH₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: F (para) Z₂: F (meta) CH₂Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: Cl (meta) CH₂ Pyrimidinyl NH—CH₂Pyrazinyl Z₁: Cl (para) CH₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: Cl (para)Z₂: Cl (meta) CH₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: F (para) Z₂: Cl(meta) CH₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: Cl (para) Z₂: F (meta) CH₂Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₃ (para) CH₂ Pyrimidinyl NH—CH₂Pyrazinyl Z₁: CH₃ (meta) CH₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₃(ortho) CH₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₃ (para) CH₂Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₃ (meta) CH₂ Pyrimidinyl NH—CH₂Pyrazinyl Z₁: CH₂—CH₃ (ortho) CH₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (para) CH₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) CH₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₂F(para) CH₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₂F (meta) CH₂ PyrimidinylNH—CH₂ Pyrazinyl Z₁: CH₂F (ortho) CH₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁:CHF₂ (para) CH₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CHF₂ (meta) CH₂Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CHF₂ (ortho) CH₂ Pyrimidinyl NH—CH₂Pyrazinyl Z₁: CF₃ (para) CH₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CF₃ (meta)CH₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CF₃ (ortho) CH₂ Pyrimidinyl NH—CH₂Pyrazinyl Z₁: CH₂—CH₂F (para) CH₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁:CH₂—CH₂F (meta) CH₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₂F (ortho)CH₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CHF₂ (para) CH₂ PyrimidinylNH—CH₂ Pyrazinyl Z₁: CH₂—CHF₂ (meta) CH₂ Pyrimidinyl NH—CH₂ PyrazinylZ₁: CH₂—CHF₂ (ortho) CH₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CF₃ (para)CH₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CF₃ (meta) CH₂ PyrimidinylNH—CH₂ Pyrazinyl Z₁: CH₂—CF₃ (ortho) CH₂ Pyrimidinyl NH—CH₂ PyrrolylNone CH₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: F (2) CH₂ Pyrimidinyl NH—CH₂Pyrrolyl Z₁: F (3) CH₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: F (2) Z₂: F (3)CH₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: Cl (2) CH₂ Pyrimidinyl NH—CH₂Pyrrolyl Z₁: Cl (3) CH₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: Cl (2) Z₂: Cl(3) CH₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: F (2) Z₂: Cl (3) CH₂ PyrimidinylNH—CH₂ Pyrrolyl Z₁: Cl (2) Z₂: F (3) CH₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁:CH₃ (2) CH₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: CH₃ (3) CH₂ PyrimidinylNH—CH₂ Pyrrolyl Z₁: CH₂—CH₃ (2) CH₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁:CH₂—CH₃ (3) CH₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (2)CH₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CH₂Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: CH₂F (2) CH₂ Pyrimidinyl NH—CH₂ PyrrolylZ₁: CH₂F (3) CH₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: CHF₂ (2) CH₂Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: CHF₂ (3) CH₂ Pyrimidinyl NH—CH₂ PyrrolylZ₁: CF₃ (2) CH₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: CF₃ (3) CH₂ PyrimidinylNH—CH₂ Pyrrolyl Z₁: CH₂—CH₂F (2) CH₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁:CH₂—CH₂F (3) CH₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CHF₂ (2) CH₂Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CHF₂ (3) CH₂ Pyrimidinyl NH—CH₂Pyrrolyl Z₁: CH₂—CF₃ (2) CH₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CF₃ (3)CH₂ Pyrimidinyl NH—CH₂ Imidazolyl None CH₂ Pyrimidinyl NH—CH₂ ImidazolylZ₁: F (2) CH₂ Pyrimidinyl NH—CH₂ Imidazolyl Z₁: F (3) CH₂ PyrimidinylNH—CH₂ Imidazolyl Z₁: F (2) Z₂: F (3) CH₂ Pyrimidinyl NH—CH₂ ImidazolylZ₁: Cl (2) CH₂ Pyrimidinyl NH—CH₂ Imidazolyl Z₁: Cl (3) CH₂ PyrimidinylNH—CH₂ Imidazolyl Z₁: Cl (2) Z₂: Cl (3) CH₂ Pyrimidinyl NH—CH₂Imidazolyl Z₁: F (2) Z₂: Cl (3) CH₂ Pyrimidinyl NH—CH₂ Imidazolyl Z₁: Cl(2) Z₂: F (3) CH₂ Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CH₃ (2) CH₂Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CH₃ (3) CH₂ Pyrimidinyl NH—CH₂Imidazolyl Z₁: CH₂—CH₃ (2) CH₂ Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₃(3) CH₂ Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CH₂ PyrimidinylNH—CH₂ Imidazolyl Z₁: CH₂F (2) CH₂ Pyrimidinyl NH—CH₂ Imidazolyl Z₁:CH₂F (3) CH₂ Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CHF₂ (2) CH₂ PyrimidinylNH—CH₂ Imidazolyl Z₁: CHF₂ (3) CH₂ Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CF₃(2) CH₂ Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CF₃ (3) CH₂ Pyrimidinyl NH—CH₂Imidazolyl Z₁: CH₂—CH₂F (2) CH₂ Pyrimidinyl NH—CH₂ Imidazolyl Z₁:CH₂—CH₂F (3) CH₂ Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CH₂—CHF₂ (2) CH₂Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CH₂—CHF₂ (3) CH₂ Pyrimidinyl NH—CH₂Imidazolyl Z₁: CH₂—CF₃ (2) CH₂ Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CH₂—CF₃(3) CH₂ Pyrimidinyl NH—CH₂ Furanyl None CH₂ Pyrimidinyl NH—CH₂ FuranylZ₁: F (2) CH₂ Pyrimidinyl NH—CH₂ Furanyl Z₁: F (3) CH₂ PyrimidinylNH—CH₂ Furanyl Z₁: F (2) Z₂: F (3) CH₂ Pyrimidinyl NH—CH₂ Furanyl Z₁: Cl(2) CH₂ Pyrimidinyl NH—CH₂ Furanyl Z₁: Cl (3) CH₂ Pyrimidinyl NH—CH₂Furanyl Z₁: Cl (2) Z₂: Cl (3) CH₂ Pyrimidinyl NH—CH₂ Furanyl Z₁: F (2)Z₂: Cl (3) CH₂ Pyrimidinyl NH—CH₂ Furanyl Z₁: Cl (2) Z₂: F (3) CH₂Pyrimidinyl NH—CH₂ Furanyl Z₁: CH₃ (2) CH₂ Pyrimidinyl NH—CH₂ FuranylZ₁: CH₃ (3) CH₂ Pyrimidinyl NH—CH₂ Furanyl Z₁: CH₂—CH₃ (2) CH₂Pyrimidinyl NH—CH₂ Furanyl Z₁: CH₂—CH₃ (3) CH₂ Pyrimidinyl NH—CH₂Furanyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂ Pyrimidinyl NH—CH₂ Furanyl Z₁:CH₂—CH₂—CH₃ or iPr (3) CH₂ Pyrimidinyl NH—CH₂ Furanyl Z₁: CH₂F (2) CH₂Pyrimidinyl NH—CH₂ Furanyl Z₁: CH₂F (3) CH₂ Pyrimidinyl NH—CH₂ FuranylZ₁: CHF₂ (2) CH₂ Pyrimidinyl NH—CH₂ Furanyl Z₁: CHF₂ (3) CH₂ PyrimidinylNH—CH₂ Furanyl Z₁: CF₃ (2) CH₂ Pyrimidinyl NH—CH₂ Furanyl Z₁: CF₃ (3)CH₂ Pyrimidinyl NH—CH₂ Furanyl Z₁: CH₂—CH₂F (2) CH₂ Pyrimidinyl NH—CH₂Furanyl Z₁: CH₂—CH₂F (3) CH₂ Pyrimidinyl NH—CH₂ Furanyl Z₁: CH₂—CHF₂ (2)CH₂ Pyrimidinyl NH—CH₂ Furanyl Z₁: CH₂—CHF₂ (3) CH₂ Pyrimidinyl NH—CH₂Furanyl Z₁: CH₂—CF₃ (2) CH₂ Pyrimidinyl NH—CH₂ Furanyl Z₁: CH₂—CF₃ (3)CH₂ Pyrimidinyl NH—CH₂ Oxazolyl None CH₂ Pyrimidinyl NH—CH₂ Oxazolyl Z₁:F (2) CH₂ Pyrimidinyl NH—CH₂ Oxazolyl Z₁: F (3) CH₂ Pyrimidinyl NH—CH₂Oxazolyl Z₁: F (2) Z₂: F (3) CH₂ Pyrimidinyl NH—CH₂ Oxazolyl Z₁: Cl (2)CH₂ Pyrimidinyl NH—CH₂ Oxazolyl Z₁: Cl (3) CH₂ Pyrimidinyl NH—CH₂Oxazolyl Z₁: Cl (2) Z₂: Cl (3) CH₂ Pyrimidinyl NH—CH₂ Oxazolyl Z₁: F (2)Z₂: Cl (3) CH₂ Pyrimidinyl NH—CH₂ Oxazolyl Z₁: Cl (2) Z₂: F (3) CH₂Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CH₃ (2) CH₂ Pyrimidinyl NH—CH₂ OxazolylZ₁: CH₃ (3) CH₂ Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₃ (2) CH₂Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₃ (3) CH₂ Pyrimidinyl NH—CH₂Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂ Pyrimidinyl NH—CH₂ Oxazolyl Z₁:CH₂—CH₂—CH₃ or iPr (3) CH₂ Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CH₂F (2) CH₂Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CH₂F (3) CH₂ Pyrimidinyl NH—CH₂ OxazolylZ₁: CHF₂ (2) CH₂ Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CHF₂ (3) CH₂Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CF₃ (2) CH₂ Pyrimidinyl NH—CH₂ OxazolylZ₁: CF₃ (3) CH₂ Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₂F (2) CH₂Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₂F (3) CH₂ Pyrimidinyl NH—CH₂Oxazolyl Z₁: CH₂—CHF₂ (2) CH₂ Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CH₂—CHF₂(3) CH₂ Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CH₂—CF₃ (2) CH₂ PyrimidinylNH—CH₂ Oxazolyl Z₁: CH₂—CF₃ (3) CH₂ Pyrimidinyl NH—CH₂ Thiophenyl NoneCH₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁: F (2) CH₂ Pyrimidinyl NH—CH₂Thiophenyl Z₁: F (3) CH₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁: F (2) Z₂: F(3) CH₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁: Cl (2) CH₂ Pyrimidinyl NH—CH₂Thiophenyl Z₁: Cl (3) CH₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁: Cl (2) Z₂:Cl (3) CH₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁: F (2) Z₂: Cl (3) CH₂Pyrimidinyl NH—CH₂ Thiophenyl Z₁: Cl (2) Z₂: F (3) CH₂ PyrimidinylNH—CH₂ Thiophenyl Z₁: CH₃ (2) CH₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CH₃(3) CH₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₃ (2) CH₂ PyrimidinylNH—CH₂ Thiophenyl Z₁: CH₂—CH₃ (3) CH₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁:CH₂—CH₂—CH₃ or iPr (2) CH₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₂—CH₃or iPr (3) CH₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CH₂F (2) CH₂Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CH₂F (3) CH₂ Pyrimidinyl NH—CH₂Thiophenyl Z₁: CHF₂ (2) CH₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CHF₂ (3)CH₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CF₃ (2) CH₂ Pyrimidinyl NH—CH₂Thiophenyl Z₁: CF₃ (3) CH₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₂F(2) CH₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₂F (3) CH₂ PyrimidinylNH—CH₂ Thiophenyl Z₁: CH₂—CHF₂ (2) CH₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁:CH₂—CHF₂ (3) CH₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CH₂—CF₃ (2) CH₂Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CH₂—CF₃ (3) CH₂ Pyrimidinyl NH—CH₂Thiazolyl None CH₂ Pyrimidinyl NH—CH₂ Thiazolyl Z₁: F (2) CH₂Pyrimidinyl NH—CH₂ Thiazolyl Z₁: F (3) CH₂ Pyrimidinyl NH—CH₂ ThiazolylZ₁: F (2) Z₂: F (3) CH₂ Pyrimidinyl NH—CH₂ Thiazolyl Z₁: Cl (2) CH₂Pyrimidinyl NH—CH₂ Thiazolyl Z₁: Cl (3) CH₂ Pyrimidinyl NH—CH₂ ThiazolylZ₁: Cl (2) Z₂: Cl (3) CH₂ Pyrimidinyl NH—CH₂ Thiazolyl Z₁: F (2) Z₂: Cl(3) CH₂ Pyrimidinyl NH—CH₂ Thiazolyl Z₁: Cl (2) Z₂: F (3) CH₂Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CH₃ (2) CH₂ Pyrimidinyl NH—CH₂Thiazolyl Z₁: CH₃ (3) CH₂ Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₃ (2)CH₂ Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₃ (3) CH₂ Pyrimidinyl NH—CH₂Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂ Pyrimidinyl NH—CH₂ ThiazolylZ₁: CH₂—CH₂—CH₃ or iPr (3) CH₂ Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CH₂F (2)CH₂ Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CH₂F (3) CH₂ Pyrimidinyl NH—CH₂Thiazolyl Z₁: CHF₂ (2) CH₂ Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CHF₂ (3) CH₂Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CF₃ (2) CH₂ Pyrimidinyl NH—CH₂Thiazolyl Z₁: CF₃ (3) CH₂ Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₂F (2)CH₂ Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₂F (3) CH₂ Pyrimidinyl NH—CH₂Thiazolyl Z₁: CH₂—CHF₂ (2) CH₂ Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CH₂—CHF₂(3) CH₂ Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CH₂—CF₃ (2) CH₂ PyrimidinylNH—CH₂ Thiazolyl Z₁: CH₂—CF₃ (3) CH₂ Pyrimidinyl NH—C(O) Phenyl None CH₂Pyrimidinyl NH—C(O) Phenyl Z₁: F (para) CH₂ Pyrimidinyl NH—C(O) phenylZ₁: F (meta) CH₂ Pyrimidinyl NH—C(O) phenyl Z₁: F (ortho) CH₂Pyrimidinyl NH—C(O) phenyl Z₁: F (para) Z₂: F (meta) CH₂ PyrimidinylNH—C(O) Phenyl Z₁: Cl (meta) CH₂ Pyrimidinyl NH—C(O) Phenyl Z₁: Cl(para) CH₂ Pyrimidinyl NH—C(O) Phenyl Z₁: Cl (para) Z₂: Cl (meta) CH₂Pyrimidinyl NH—C(O) Phenyl Z₁: F (para) Z₂: Cl (meta) CH₂ PyrimidinylNH—C(O) Phenyl Z₁: Cl (para) Z₂: F (meta) CH₂ Pyrimidinyl NH—C(O) PhenylZ₁: CH₃ (para) CH₂ Pyrimidinyl NH—C(O) Phenyl Z₁: CH₃ (meta) CH₂Pyrimidinyl NH—C(O) Phenyl Z₁: CH₃ (ortho) CH₂ Pyrimidinyl NH—C(O)Phenyl Z₁: CH₂—CH₃ (para) CH₂ Pyrimidinyl NH—C(O) Phenyl Z₁: CH₂—CH₃(meta) CH₂ Pyrimidinyl NH—C(O) Phenyl Z₁: CH₂—CH₃ (ortho) CH₂Pyrimidinyl NH—C(O) Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CH₂ PyrimidinylNH—C(O) Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CH₂ Pyrimidinyl NH—C(O)Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyrimidinyl NH—C(O) Phenyl Z₁:CH₂F (para) CH₂ Pyrimidinyl NH—C(O) Phenyl Z₁: CH₂F (meta) CH₂Pyrimidinyl NH—C(O) Phenyl Z₁: CH₂F (ortho) CH₂ Pyrimidinyl NH—C(O)Phenyl Z₁: CHF₂ (para) CH₂ Pyrimidinyl NH—C(O) Phenyl Z₁: CHF₂ (meta)CH₂ Pyrimidinyl NH—C(O) Phenyl Z₁: CHF₂ (ortho) CH₂ Pyrimidinyl NH—C(O)Phenyl Z₁: CF₃ (para) CH₂ Pyrimidinyl NH—C(O) Phenyl Z₁: CF₃ (meta) CH₂Pyrimidinyl NH—C(O) Phenyl Z₁: CF₃ (ortho) CH₂ Pyrimidinyl NH—C(O)Phenyl Z₁: CH₂—CH₂F (para) CH₂ Pyrimidinyl NH—C(O) Phenyl Z₁: CH₂—CH₂F(meta) CH₂ Pyrimidinyl NH—C(O) Phenyl Z₁: CH₂—CH₂F (ortho) CH₂Pyrimidinyl NH—C(O) Phenyl Z₁: CH₂—CHF₂ (para) CH₂ Pyrimidinyl NH—C(O)Phenyl Z₁: CH₂—CHF₂ (meta) CH₂ Pyrimidinyl NH—C(O) Phenyl Z₁: CH₂—CHF₂(ortho) CH₂ Pyrimidinyl NH—C(O) Phenyl Z₁: CH₂—CF₃ (para) CH₂Pyrimidinyl NH—C(O) Phenyl Z₁: CH₂—CF₃ (meta) CH₂ Pyrimidinyl NH—C(O)Phenyl Z₁: CH₂—CF₃ (ortho) CH₂ Pyrimidinyl NH—C(O) Pyridinyl None CH₂Pyrimidinyl NH—C(O) Pyridinyl Z₁: F (para) CH₂ Pyrimidinyl NH—C(O)Pyridinyl Z₁: F (meta) CH₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: F (ortho)CH₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: F (para) Z₂: F (meta) CH₂Pyrimidinyl NH—C(O) Pyridinyl Z₁: Cl (meta) CH₂ Pyrimidinyl NH—C(O)Pyridinyl Z₁: Cl (para) CH₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: Cl (para)Z₂: Cl (meta) CH₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: F (para) Z₂: Cl(meta) CH₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: Cl (para) Z₂: F (meta) CH₂Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₃ (para) CH₂ Pyrimidinyl NH—C(O)Pyridinyl Z₁: CH₃ (meta) CH₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₃(ortho) CH₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₃ (para) CH₂Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₃ (meta) CH₂ Pyrimidinyl NH—C(O)Pyridinyl Z₁: CH₂—CH₃ (ortho) CH₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁:CH₂—CH₂—CH₃ or iPr (para) CH₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) CH₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂F(para) CH₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂F (meta) CH₂ PyrimidinylNH—C(O) Pyridinyl Z₁: CH₂F (ortho) CH₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁:CHF₂ (para) CH₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: CHF₂ (meta) CH₂Pyrimidinyl NH—C(O) Pyridinyl Z₁: CHF₂ (ortho) CH₂ Pyrimidinyl NH—C(O)Pyridinyl Z₁: CF₃ (para) CH₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: CF₃(meta) CH₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: CF₃ (ortho) CH₂ PyrimidinylNH—C(O) Pyridinyl Z₁: CH₂—CH₂F (para) CH₂ Pyrimidinyl NH—C(O) PyridinylZ₁: CH₂—CH₂F (meta) CH₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₂F(ortho) CH₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂—CHF₂ (para) CH₂Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂—CHF₂ (meta) CH₂ PyrimidinylNH—C(O) Pyridinyl Z₁: CH₂—CHF₂ (ortho) CH₂ Pyrimidinyl NH—C(O) PyridinylZ₁: CH₂—CF₃ (para) CH₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂—CF₃ (meta)CH₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂—CF₃ (ortho) CH₂ PyrimidinylNH—C(O) Pyrimidinyl None CH₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: F(para) CH₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: F (meta) CH₂ PyrimidinylNH—C(O) Pyrimidinyl Z₁: F (ortho) CH₂ Pyrimidinyl NH—C(O) PyrimidinylZ₁: F (para) Z₂: F (meta) CH₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: Cl(meta) CH₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: Cl (para) CH₂ PyrimidinylNH—C(O) Pyrimidinyl Z₁: Cl (para) Z₂: Cl (meta) CH₂ Pyrimidinyl NH—C(O)Pyrimidinyl Z₁: F (para) Z₂: Cl (meta) CH₂ Pyrimidinyl NH—C(O)Pyrimidinyl Z₁: Cl (para) Z₂: F (meta) CH₂ Pyrimidinyl NH—C(O)Pyrimidinyl Z₁: CH₃ (para) CH₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₃(meta) CH₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₃ (ortho) CH₂Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CH₃ (para) CH₂ PyrimidinylNH—C(O) Pyrimidinyl Z₁: CH₂—CH₃ (meta) CH₂ Pyrimidinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CH₃ (ortho) CH₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (para) CH₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) CH₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₂F(para) CH₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₂F (meta) CH₂Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₂F (ortho) CH₂ Pyrimidinyl NH—C(O)Pyrimidinyl Z₁: CHF₂ (para) CH₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CHF₂(meta) CH₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CHF₂ (ortho) CH₂Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CF₃ (para) CH₂ Pyrimidinyl NH—C(O)Pyrimidinyl Z₁: CF₃ (meta) CH₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CF₃(ortho) CH₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CH₂F (para) CH₂Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CH₂F (meta) CH₂ PyrimidinylNH—C(O) Pyrimidinyl Z₁: CH₂—CH₂F (ortho) CH₂ Pyrimidinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CHF₂ (para) CH₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CHF₂ (meta) CH₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CHF₂ (ortho)CH₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CF₃ (para) CH₂ PyrimidinylNH—C(O) Pyrimidinyl Z₁: CH₂—CF₃ (meta) CH₂ Pyrimidinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CF₃ (ortho) CH₂ Pyrimidinyl NH—C(O) Pyrazinyl NoneCH₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: F (para) CH₂ Pyrimidinyl NH—C(O)Pyrazinyl Z₁: F (meta) CH₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: F (ortho)CH₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: F (para) Z₂: F (meta) CH₂Pyrimidinyl NH—C(O) Pyrazinyl Z₁: Cl (meta) CH₂ Pyrimidinyl NH—C(O)Pyrazinyl Z₁: Cl (para) CH₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: Cl (para)Z₂: Cl (meta) CH₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: F (para) Z₂: Cl(meta) CH₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: Cl (para) Z₂: F (meta) CH₂Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₃ (para) CH₂ Pyrimidinyl NH—C(O)Pyrazinyl Z₁: CH₃ (meta) CH₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₃(ortho) CH₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₂—CH₃ (para) CH₂Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₂—CH₃ (meta) CH₂ Pyrimidinyl NH—C(O)Pyrazinyl Z₁: CH₂—CH₃ (ortho) CH₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (para) CH₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) CH₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₂F(para) CH₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₂F (meta) CH₂ PyrimidinylNH—C(O) Pyrazinyl Z₁: CH₂F (ortho) CH₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁:CHF₂ (para) CH₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CHF₂ (meta) CH₂Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CHF₂ (ortho) CH₂ Pyrimidinyl NH—C(O)Pyrazinyl Z₁: CF₃ (para) CH₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CF₃(meta) CH₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CF₃ (ortho) CH₂ PyrimidinylNH—C(O) Pyrazinyl Z₁: CH₂—CH₂F (para) CH₂ Pyrimidinyl NH—C(O) PyrazinylZ₁: CH₂—CH₂F (meta) CH₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₂—CH₂F(ortho) CH₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₂—CHF₂ (para) CH₂Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₂—CHF₂ (meta) CH₂ PyrimidinylNH—C(O) Pyrazinyl Z₁: CH₂—CHF₂ (ortho) CH₂ Pyrimidinyl NH—C(O) PyrazinylZ₁: CH₂—CF₃ (para) CH₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₂—CF₃ (meta)CH₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₂—CF₃ (ortho) CH₂ PyrimidinylNH—C(O) Pyrrolyl None CH₂ Pyrimidinyl NH—C(O) Pyrrolyl Z₁: F (2) CH₂Pyrimidinyl NH—C(O) Pyrrolyl Z₁: F (3) CH₂ Pyrimidinyl NH—C(O) PyrrolylZ₁: F (2) Z₂: F (3) CH₂ Pyrimidinyl NH—C(O) Pyrrolyl Z₁: Cl (2) CH₂Pyrimidinyl NH—C(O) Pyrrolyl Z₁: Cl (3) CH₂ Pyrimidinyl NH—C(O) PyrrolylZ₁: Cl (2) Z₂: Cl (3) CH₂ Pyrimidinyl NH—C(O) Pyrrolyl Z₁: F (2) Z₂: Cl(3) CH₂ Pyrimidinyl NH—C(O) Pyrrolyl Z₁: Cl (2) Z₂: F (3) CH₂Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CH₃ (2) CH₂ Pyrimidinyl NH—C(O)Pyrrolyl Z₁: CH₃ (3) CH₂ Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₃ (2)CH₂ Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₃ (3) CH₂ Pyrimidinyl NH—C(O)Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂ Pyrimidinyl NH—C(O) Pyrrolyl Z₁:CH₂—CH₂—CH₃ or iPr (3) CH₂ Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CH₂F (2) CH₂Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CH₂F (3) CH₂ Pyrimidinyl NH—C(O)Pyrrolyl Z₁: CHF₂ (2) CH₂ Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CHF₂ (3) CH₂Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CF₃ (2) CH₂ Pyrimidinyl NH—C(O)Pyrrolyl Z₁: CF₃ (3) CH₂ Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₂F (2)CH₂ Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₂F (3) CH₂ PyrimidinylNH—C(O) Pyrrolyl Z₁: CH₂—CHF₂ (2) CH₂ Pyrimidinyl NH—C(O) Pyrrolyl Z₁:CH₂—CHF₂ (3) CH₂ Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CH₂—CF₃ (2) CH₂Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CH₂—CF₃ (3) CH₂ Pyrimidinyl NH—C(O)Imidazolyl None CH₂ Pyrimidinyl NH—C(O) Imidazolyl Z₁: F (2) CH₂Pyrimidinyl NH—C(O) Imidazolyl Z₁: F (3) CH₂ Pyrimidinyl NH—C(O)Imidazolyl Z₁: F (2) Z₂: F (3) CH₂ Pyrimidinyl NH—C(O) Imidazolyl Z₁: Cl(2) CH₂ Pyrimidinyl NH—C(O) Imidazolyl Z₁: Cl (3) CH₂ PyrimidinylNH—C(O) Imidazolyl Z₁: Cl (2) Z₂: Cl (3) CH₂ Pyrimidinyl NH—C(O)Imidazolyl Z₁: F (2) Z₂: Cl (3) CH₂ Pyrimidinyl NH—C(O) Imidazolyl Z₁:Cl (2) Z₂: F (3) CH₂ Pyrimidinyl NH—C(O) Imidazolyl Z₁: CH₃ (2) CH₂Pyrimidinyl NH—C(O) Imidazolyl Z₁: CH₃ (3) CH₂ Pyrimidinyl NH—C(O)Imidazolyl Z₁: CH₂—CH₃ (2) CH₂ Pyrimidinyl NH—C(O) Imidazolyl Z₁:CH₂—CH₃ (3) CH₂ Pyrimidinyl NH—C(O) Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr(2) CH₂ Pyrimidinyl NH—C(O) Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CH₂Pyrimidinyl NH—C(O) Imidazolyl Z₁: CH₂F (2) CH₂ Pyrimidinyl NH—C(O)Imidazolyl Z₁: CH₂F (3) CH₂ Pyrimidinyl NH—C(O) Imidazolyl Z₁: CHF₂ (2)CH₂ Pyrimidinyl NH—C(O) Imidazolyl Z₁: CHF₂ (3) CH₂ Pyrimidinyl NH—C(O)Imidazolyl Z₁: CF₃ (2) CH₂ Pyrimidinyl NH—C(O) Imidazolyl Z₁: CF₃ (3)CH₂ Pyrimidinyl NH—C(O) Imidazolyl Z₁: CH₂—CH₂F (2) CH₂ PyrimidinylNH—C(O) Imidazolyl Z₁: CH₂—CH₂F (3) CH₂ Pyrimidinyl NH—C(O) ImidazolylZ₁: CH₂—CHF₂ (2) CH₂ Pyrimidinyl NH—C(O) Imidazolyl Z₁: CH₂—CHF₂ (3) CH₂Pyrimidinyl NH—C(O) Imidazolyl Z₁: CH₂—CF₃ (2) CH₂ Pyrimidinyl NH—C(O)Imidazolyl Z₁: CH₂—CF₃ (3) CH₂ Pyrimidinyl NH—C(O) Furanyl None CH₂Pyrimidinyl NH—C(O) Furanyl Z₁: F (2) CH₂ Pyrimidinyl NH—C(O) FuranylZ₁: F (3) CH₂ Pyrimidinyl NH—C(O) Furanyl Z₁: F (2) Z₂: F (3) CH₂Pyrimidinyl NH—C(O) Furanyl Z₁: Cl (2) CH₂ Pyrimidinyl NH—C(O) FuranylZ₁: Cl (3) CH₂ Pyrimidinyl NH—C(O) Furanyl Z₁: Cl (2) Z₂: Cl (3) CH₂Pyrimidinyl NH—C(O) Furanyl Z₁: F (2) Z₂: Cl (3) CH₂ Pyrimidinyl NH—C(O)Furanyl Z₁: Cl (2) Z₂: F (3) CH₂ Pyrimidinyl NH—C(O) Furanyl Z₁: CH₃ (2)CH₂ Pyrimidinyl NH—C(O) Furanyl Z₁: CH₃ (3) CH₂ Pyrimidinyl NH—C(O)Furanyl Z₁: CH₂—CH₃ (2) CH₂ Pyrimidinyl NH—C(O) Furanyl Z₁: CH₂—CH₃ (3)CH₂ Pyrimidinyl NH—C(O) Furanyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂Pyrimidinyl NH—C(O) Furanyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CH₂ PyrimidinylNH—C(O) Furanyl Z₁: CH₂F (2) CH₂ Pyrimidinyl NH—C(O) Furanyl Z₁: CH₂F(3) CH₂ Pyrimidinyl NH—C(O) Furanyl Z₁: CHF₂ (2) CH₂ Pyrimidinyl NH—C(O)Furanyl Z₁: CHF₂ (3) CH₂ Pyrimidinyl NH—C(O) Furanyl Z₁: CF₃ (2) CH₂Pyrimidinyl NH—C(O) Furanyl Z₁: CF₃ (3) CH₂ Pyrimidinyl NH—C(O) FuranylZ₁: CH₂—CH₂F (2) CH₂ Pyrimidinyl NH—C(O) Furanyl Z₁: CH₂—CH₂F (3) CH₂Pyrimidinyl NH—C(O) Furanyl Z₁: CH₂—CHF₂ (2) CH₂ Pyrimidinyl NH—C(O)Furanyl Z₁: CH₂—CHF₂ (3) CH₂ Pyrimidinyl NH—C(O) Furanyl Z₁: CH₂—CF₃ (2)CH₂ Pyrimidinyl NH—C(O) Furanyl Z₁: CH₂—CF₃ (3) CH₂ Pyrimidinyl NH—C(O)Oxazolyl None CH₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁: F (2) CH₂ PyrimidinylNH—C(O) Oxazolyl Z₁: F (3) CH₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁: F (2)Z₂: F (3) CH₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁: Cl (2) CH₂ PyrimidinylNH—C(O) Oxazolyl Z₁: Cl (3) CH₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁: Cl (2)Z₂: Cl (3) CH₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁: F (2) Z₂: Cl (3) CH₂Pyrimidinyl NH—C(O) Oxazolyl Z₁: Cl (2) Z₂: F (3) CH₂ PyrimidinylNH—C(O) Oxazolyl Z₁: CH₃ (2) CH₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁: CH₃(3) CH₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₃ (2) CH₂ PyrimidinylNH—C(O) Oxazolyl Z₁: CH₂—CH₃ (3) CH₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁:CH₂—CH₂—CH₃ or iPr (2) CH₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₂—CH₃or iPr (3) CH₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁: CH₂F (2) CH₂ PyrimidinylNH—C(O) Oxazolyl Z₁: CH₂F (3) CH₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁: CHF₂(2) CH₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁: CHF₂ (3) CH₂ PyrimidinylNH—C(O) Oxazolyl Z₁: CF₃ (2) CH₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁: CF₃(3) CH₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₂F (2) CH₂ PyrimidinylNH—C(O) Oxazolyl Z₁: CH₂—CH₂F (3) CH₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁:CH₂—CHF₂ (2) CH₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁: CH₂—CHF₂ (3) CH₂Pyrimidinyl NH—C(O) Oxazolyl Z₁: CH₂—CF₃ (2) CH₂ Pyrimidinyl NH—C(O)Oxazolyl Z₁: CH₂—CF₃ (3) CH₂ Pyrimidinyl NH—C(O) Thiophenyl None CH₂Pyrimidinyl NH—C(O) Thiophenyl Z₁: F (2) CH₂ Pyrimidinyl NH—C(O)Thiophenyl Z₁: F (3) CH₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁: F (2) Z₂: F(3) CH₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁: Cl (2) CH₂ PyrimidinylNH—C(O) Thiophenyl Z₁: Cl (3) CH₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁: Cl(2) Z₂: Cl (3) CH₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁: F (2) Z₂: Cl (3)CH₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁: Cl (2) Z₂: F (3) CH₂ PyrimidinylNH—C(O) Thiophenyl Z₁: CH₃ (2) CH₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁:CH₃ (3) CH₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁: CH₂—CH₃ (2) CH₂Pyrimidinyl NH—C(O) Thiophenyl Z₁: CH₂—CH₃ (3) CH₂ Pyrimidinyl NH—C(O)Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂ Pyrimidinyl NH—C(O) ThiophenylZ₁: CH₂—CH₂—CH₃ or iPr (3) CH₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁: CH₂F(2) CH₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁: CH₂F (3) CH₂ PyrimidinylNH—C(O) Thiophenyl Z₁: CHF₂ (2) CH₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁:CHF₂ (3) CH₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁: CF₃ (2) CH₂ PyrimidinylNH—C(O) Thiophenyl Z₁: CF₃ (3) CH₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁:CH₂—CH₂F (2) CH₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁: CH₂—CH₂F (3) CH₂Pyrimidinyl NH—C(O) Thiophenyl Z₁: CH₂—CHF₂ (2) CH₂ Pyrimidinyl NH—C(O)Thiophenyl Z₁: CH₂—CHF₂ (3) CH₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁:CH₂—CF₃ (2) CH₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁: CH₂—CF₃ (3) CH₂Pyrimidinyl NH—C(O) Thiazolyl None CH₂ Pyrimidinyl NH—C(O) Thiazolyl Z₁:F (2) CH₂ Pyrimidinyl NH—C(O) Thiazolyl Z₁: F (3) CH₂ PyrimidinylNH—C(O) Thiazolyl Z₁: F (2) Z₂: F (3) CH₂ Pyrimidinyl NH—C(O) ThiazolylZ₁: Cl (2) CH₂ Pyrimidinyl NH—C(O) Thiazolyl Z₁: Cl (3) CH₂ PyrimidinylNH—C(O) Thiazolyl Z₁: Cl (2) Z₂: Cl (3) CH₂ Pyrimidinyl NH—C(O)Thiazolyl Z₁: F (2) Z₂: Cl (3) CH₂ Pyrimidinyl NH—C(O) Thiazolyl Z₁: Cl(2) Z₂: F (3) CH₂ Pyrimidinyl NH—C(O) Thiazolyl Z₁: CH₃ (2) CH₂Pyrimidinyl NH—C(O) Thiazolyl Z₁: CH₃ (3) CH₂ Pyrimidinyl NH—C(O)Thiazolyl Z₁: CH₂—CH₃ (2) CH₂ Pyrimidinyl NH—C(O) Thiazolyl Z₁: CH₂—CH₃(3) CH₂ Pyrimidinyl NH—C(O) Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂Pyrimidinyl NH—C(O) Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CH₂ PyrimidinylNH—C(O) Thiazolyl Z₁: CH₂F (2) CH₂ Pyrimidinyl NH—C(O) Thiazolyl Z₁:CH₂F (3) CH₂ Pyrimidinyl NH—C(O) Thiazolyl Z₁: CHF₂ (2) CH₂ PyrimidinylNH—C(O) Thiazolyl Z₁: CHF₂ (3) CH₂ Pyrimidinyl NH—C(O) Thiazolyl Z₁: CF₃(2) CH₂ Pyrimidinyl NH—C(O) Thiazolyl Z₁: CF₃ (3) CH₂ PyrimidinylNH—C(O) Thiazolyl Z₁: CH₂—CH₂F (2) CH₂ Pyrimidinyl NH—C(O) Thiazolyl Z₁:CH₂—CH₂F (3) CH₂ Pyrimidinyl NH—C(O) Thiazolyl Z₁: CH₂—CHF₂ (2) CH₂Pyrimidinyl NH—C(O) Thiazolyl Z₁: CH₂—CHF₂ (3) CH₂ Pyrimidinyl NH—C(O)Thiazolyl Z₁: CH₂—CF₃ (2) CH₂ Pyrimidinyl NH—C(O) Thiazolyl Z₁: CH₂—CF₃(3) CH₂ Pyrimidinyl NH—SO₂ Phenyl None CH₂ Pyrimidinyl NH—SO₂ Phenyl Z₁:F (para) CH₂ Pyrimidinyl NH—SO₂ phenyl Z₁: F (meta) CH₂ PyrimidinylNH—SO₂ phenyl Z₁: F (ortho) CH₂ Pyrimidinyl NH—SO₂ phenyl Z₁: F (para)Z₂: F (meta) CH₂ Pyrimidinyl NH—SO₂ Phenyl Z₁: Cl (meta) CH₂ PyrimidinylNH—SO₂ Phenyl Z₁: Cl (para) CH₂ Pyrimidinyl NH—SO₂ Phenyl Z₁: Cl (para)Z₂: Cl (meta) CH₂ Pyrimidinyl NH—SO₂ Phenyl Z₁: F (para) Z₂: Cl (meta)CH₂ Pyrimidinyl NH—SO₂ Phenyl Z₁: Cl (para) Z₂: F (meta) CH₂ PyrimidinylNH—SO₂ Phenyl Z₁: CH₃ (para) CH₂ Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₃(meta) CH₂ Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₃ (ortho) CH₂ PyrimidinylNH—SO₂ Phenyl Z₁: CH₂—CH₃ (para) CH₂ Pyrimidinyl NH—SO₂ Phenyl Z₁:CH₂—CH₃ (meta) CH₂ Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₂—CH₃ (ortho) CH₂Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CH₂ PyrimidinylNH—SO₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CH₂ Pyrimidinyl NH—SO₂Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyrimidinyl NH—SO₂ Phenyl Z₁:CH₂F (para) CH₂ Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₂F (meta) CH₂Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₂F (ortho) CH₂ Pyrimidinyl NH—SO₂ PhenylZ₁: CHF₂ (para) CH₂ Pyrimidinyl NH—SO₂ Phenyl Z₁: CHF₂ (meta) CH₂Pyrimidinyl NH—SO₂ Phenyl Z₁: CHF₂ (ortho) CH₂ Pyrimidinyl NH—SO₂ PhenylZ₁: CF₃ (para) CH₂ Pyrimidinyl NH—SO₂ Phenyl Z₁: CF₃ (meta) CH₂Pyrimidinyl NH—SO₂ Phenyl Z₁: CF₃ (ortho) CH₂ Pyrimidinyl NH—SO₂ PhenylZ₁: CH₂—CH₂F (para) CH₂ Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂F (meta)CH₂ Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂F (ortho) CH₂ PyrimidinylNH—SO₂ Phenyl Z₁: CH₂—CHF₂ (para) CH₂ Pyrimidinyl NH—SO₂ Phenyl Z₁:CH₂—CHF₂ (meta) CH₂ Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₂—CHF₂ (ortho) CH₂Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₂—CF₃ (para) CH₂ Pyrimidinyl NH—SO₂Phenyl Z₁: CH₂—CF₃ (meta) CH₂ Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₂—CF₃(ortho) CH₂ Pyrimidinyl NH—SO₂ Pyridinyl None CH₂ Pyrimidinyl NH—SO₂Pyridinyl Z₁: F (para) CH₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁: F (meta) CH₂Pyrimidinyl NH—SO₂ Pyridinyl Z₁: F (ortho) CH₂ Pyrimidinyl NH—SO₂Pyridinyl Z₁: F (para) Z₂: F (meta) CH₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁:Cl (meta) CH₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁: Cl (para) CH₂ PyrimidinylNH—SO₂ Pyridinyl Z₁: Cl (para) Z₂: Cl (meta) CH₂ Pyrimidinyl NH—SO₂Pyridinyl Z₁: F (para) Z₂: Cl (meta) CH₂ Pyrimidinyl NH—SO₂ PyridinylZ₁: Cl (para) Z₂: F (meta) CH₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₃(para) CH₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₃ (meta) CH₂ PyrimidinylNH—SO₂ Pyridinyl Z₁: CH₃ (ortho) CH₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁:CH₂—CH₃ (para) CH₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₃ (meta) CH₂Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₃ (ortho) CH₂ Pyrimidinyl NH—SO₂Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CH₂ Pyrimidinyl NH—SO₂ PyridinylZ₁: CH₂—CH₂—CH₃ or iPr (meta) CH₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₂F(para) CH₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₂F (meta) CH₂ PyrimidinylNH—SO₂ Pyridinyl Z₁: CH₂F (ortho) CH₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁:CHF₂ (para) CH₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CHF₂ (meta) CH₂Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CHF₂ (ortho) CH₂ Pyrimidinyl NH—SO₂Pyridinyl Z₁: CF₃ (para) CH₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CF₃ (meta)CH₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CF₃ (ortho) CH₂ Pyrimidinyl NH—SO₂Pyridinyl Z₁: CH₂—CH₂F (para) CH₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁:CH₂—CH₂F (meta) CH₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₂F (ortho)CH₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₂—CHF₂ (para) CH₂ PyrimidinylNH—SO₂ Pyridinyl Z₁: CH₂—CHF₂ (meta) CH₂ Pyrimidinyl NH—SO₂ PyridinylZ₁: CH₂—CHF₂ (ortho) CH₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₂—CF₃ (para)CH₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₂—CF₃ (meta) CH₂ PyrimidinylNH—SO₂ Pyridinyl Z₁: CH₂—CF₃ (ortho) CH₂ Pyrimidinyl NH—SO₂ PyrimidinylNone CH₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: F (para) CH₂ PyrimidinylNH—SO₂ Pyrimidinyl Z₁: F (meta) CH₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: F(ortho) CH₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: F (para) Z₂: F (meta) CH₂Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: Cl (meta) CH₂ Pyrimidinyl NH—SO₂Pyrimidinyl Z₁: Cl (para) CH₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: Cl(para) Z₂: Cl (meta) CH₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: F (para) Z₂:Cl (meta) CH₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: Cl (para) Z₂: F (meta)CH₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₃ (para) CH₂ Pyrimidinyl NH—SO₂Pyrimidinyl Z₁: CH₃ (meta) CH₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₃(ortho) CH₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₃ (para) CH₂Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₃ (meta) CH₂ Pyrimidinyl NH—SO₂Pyrimidinyl Z₁: CH₂—CH₃ (ortho) CH₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (para) CH₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) CH₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₂F(para) CH₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₂F (meta) CH₂Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₂F (ortho) CH₂ Pyrimidinyl NH—SO₂Pyrimidinyl Z₁: CHF₂ (para) CH₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CHF₂(meta) CH₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CHF₂ (ortho) CH₂Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CF₃ (para) CH₂ Pyrimidinyl NH—SO₂Pyrimidinyl Z₁: CF₃ (meta) CH₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CF₃(ortho) CH₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂F (para) CH₂Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂F (meta) CH₂ PyrimidinylNH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂F (ortho) CH₂ Pyrimidinyl NH—SO₂Pyrimidinyl Z₁: CH₂—CHF₂ (para) CH₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁:CH₂—CHF₂ (meta) CH₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CHF₂ (ortho)CH₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CF₃ (para) CH₂ PyrimidinylNH—SO₂ Pyrimidinyl Z₁: CH₂—CF₃ (meta) CH₂ Pyrimidinyl NH—SO₂ PyrimidinylZ₁: CH₂—CF₃ (ortho) CH₂ Pyrimidinyl NH—SO₂ Pyrazinyl None CH₂Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: F (para) CH₂ Pyrimidinyl NH—SO₂Pyrazinyl Z₁: F (meta) CH₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: F (ortho)CH₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: F (para) Z₂: F (meta) CH₂Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: Cl (meta) CH₂ Pyrimidinyl NH—SO₂Pyrazinyl Z₁: Cl (para) CH₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: Cl (para)Z₂: Cl (meta) CH₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: F (para) Z₂: Cl(meta) CH₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: Cl (para) Z₂: F (meta) CH₂Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₃ (para) CH₂ Pyrimidinyl NH—SO₂Pyrazinyl Z₁: CH₃ (meta) CH₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₃(ortho) CH₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₃ (para) CH₂Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₃ (meta) CH₂ Pyrimidinyl NH—SO₂Pyrazinyl Z₁: CH₂—CH₃ (ortho) CH₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (para) CH₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) CH₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₂F(para) CH₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₂F (meta) CH₂ PyrimidinylNH—SO₂ Pyrazinyl Z₁: CH₂F (ortho) CH₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁:CHF₂ (para) CH₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CHF₂ (meta) CH₂Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CHF₂ (ortho) CH₂ Pyrimidinyl NH—SO₂Pyrazinyl Z₁: CF₃ (para) CH₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CF₃ (meta)CH₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CF₃ (ortho) CH₂ Pyrimidinyl NH—SO₂Pyrazinyl Z₁: CH₂—CH₂F (para) CH₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁:CH₂—CH₂F (meta) CH₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₂F (ortho)CH₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CHF₂ (para) CH₂ PyrimidinylNH—SO₂ Pyrazinyl Z₁: CH₂—CHF₂ (meta) CH₂ Pyrimidinyl NH—SO₂ PyrazinylZ₁: CH₂—CHF₂ (ortho) CH₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CF₃ (para)CH₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CF₃ (meta) CH₂ PyrimidinylNH—SO₂ Pyrazinyl Z₁: CH₂—CF₃ (ortho) CH₂ Pyrimidinyl NH—SO₂ PyrrolylNone CH₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: F (2) CH₂ Pyrimidinyl NH—SO₂Pyrrolyl Z₁: F (3) CH₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: F (2) Z₂: F (3)CH₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: Cl (2) CH₂ Pyrimidinyl NH—SO₂Pyrrolyl Z₁: Cl (3) CH₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: Cl (2) Z₂: Cl(3) CH₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: F (2) Z₂: Cl (3) CH₂ PyrimidinylNH—SO₂ Pyrrolyl Z₁: Cl (2) Z₂: F (3) CH₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁:CH₃ (2) CH₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: CH₃ (3) CH₂ PyrimidinylNH—SO₂ Pyrrolyl Z₁: CH₂—CH₃ (2) CH₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁:CH₂—CH₃ (3) CH₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (2)CH₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CH₂Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: CH₂F (2) CH₂ Pyrimidinyl NH—SO₂ PyrrolylZ₁: CH₂F (3) CH₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: CHF₂ (2) CH₂Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: CHF₂ (3) CH₂ Pyrimidinyl NH—SO₂ PyrrolylZ₁: CF₃ (2) CH₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: CF₃ (3) CH₂ PyrimidinylNH—SO₂ Pyrrolyl Z₁: CH₂—CH₂F (2) CH₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁:CH₂—CH₂F (3) CH₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CHF₂ (2) CH₂Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CHF₂ (3) CH₂ Pyrimidinyl NH—SO₂Pyrrolyl Z₁: CH₂—CF₃ (2) CH₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CF₃ (3)CH₂ Pyrimidinyl NH—SO₂ Imidazolyl None CH₂ Pyrimidinyl NH—SO₂ ImidazolylZ₁: F (2) CH₂ Pyrimidinyl NH—SO₂ Imidazolyl Z₁: F (3) CH₂ PyrimidinylNH—SO₂ Imidazolyl Z₁: F (2) Z₂: F (3) CH₂ Pyrimidinyl NH—SO₂ ImidazolylZ₁: Cl (2) CH₂ Pyrimidinyl NH—SO₂ Imidazolyl Z₁: Cl (3) CH₂ PyrimidinylNH—SO₂ Imidazolyl Z₁: Cl (2) Z₂: Cl (3) CH₂ Pyrimidinyl NH—SO₂Imidazolyl Z₁: F (2) Z₂: Cl (3) CH₂ Pyrimidinyl NH—SO₂ Imidazolyl Z₁: Cl(2) Z₂: F (3) CH₂ Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CH₃ (2) CH₂Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CH₃ (3) CH₂ Pyrimidinyl NH—SO₂Imidazolyl Z₁: CH₂—CH₃ (2) CH₂ Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₃(3) CH₂ Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CH₂ PyrimidinylNH—SO₂ Imidazolyl Z₁: CH₂F (2) CH₂ Pyrimidinyl NH—SO₂ Imidazolyl Z₁:CH₂F (3) CH₂ Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CHF₂ (2) CH₂ PyrimidinylNH—SO₂ Imidazolyl Z₁: CHF₂ (3) CH₂ Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CF₃(2) CH₂ Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CF₃ (3) CH₂ Pyrimidinyl NH—SO₂Imidazolyl Z₁: CH₂—CH₂F (2) CH₂ Pyrimidinyl NH—SO₂ Imidazolyl Z₁:CH₂—CH₂F (3) CH₂ Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CH₂—CHF₂ (2) CH₂Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CH₂—CHF₂ (3) CH₂ Pyrimidinyl NH—SO₂Imidazolyl Z₁: CH₂—CF₃ (2) CH₂ Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CH₂—CF₃(3) CH₂ Pyrimidinyl NH—SO₂ Furanyl None CH₂ Pyrimidinyl NH—SO₂ FuranylZ₁: F (2) CH₂ Pyrimidinyl NH—SO₂ Furanyl Z₁: F (3) CH₂ PyrimidinylNH—SO₂ Furanyl Z₁: F (2) Z₂: F (3) CH₂ Pyrimidinyl NH—SO₂ Furanyl Z₁: Cl(2) CH₂ Pyrimidinyl NH—SO₂ Furanyl Z₁: Cl (3) CH₂ Pyrimidinyl NH—SO₂Furanyl Z₁: Cl (2) Z₂: Cl (3) CH₂ Pyrimidinyl NH—SO₂ Furanyl Z₁: F (2)Z₂: Cl (3) CH₂ Pyrimidinyl NH—SO₂ Furanyl Z₁: Cl (2) Z₂: F (3) CH₂Pyrimidinyl NH—SO₂ Furanyl Z₁: CH₃ (2) CH₂ Pyrimidinyl NH—SO₂ FuranylZ₁: CH₃ (3) CH₂ Pyrimidinyl NH—SO₂ Furanyl Z₁: CH₂—CH₃ (2) CH₂Pyrimidinyl NH—SO₂ Furanyl Z₁: CH₂—CH₃ (3) CH₂ Pyrimidinyl NH—SO₂Furanyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂ Pyrimidinyl NH—SO₂ Furanyl Z₁:CH₂—CH₂—CH₃ or iPr (3) CH₂ Pyrimidinyl NH—SO₂ Furanyl Z₁: CH₂F (2) CH₂Pyrimidinyl NH—SO₂ Furanyl Z₁: CH₂F (3) CH₂ Pyrimidinyl NH—SO₂ FuranylZ₁: CHF₂ (2) CH₂ Pyrimidinyl NH—SO₂ Furanyl Z₁: CHF₂ (3) CH₂ PyrimidinylNH—SO₂ Furanyl Z₁: CF₃ (2) CH₂ Pyrimidinyl NH—SO₂ Furanyl Z₁: CF₃ (3)CH₂ Pyrimidinyl NH—SO₂ Furanyl Z₁: CH₂—CH₂F (2) CH₂ Pyrimidinyl NH—SO₂Furanyl Z₁: CH₂—CH₂F (3) CH₂ Pyrimidinyl NH—SO₂ Furanyl Z₁: CH₂—CHF₂ (2)CH₂ Pyrimidinyl NH—SO₂ Furanyl Z₁: CH₂—CHF₂ (3) CH₂ Pyrimidinyl NH—SO₂Furanyl Z₁: CH₂—CF₃ (2) CH₂ Pyrimidinyl NH—SO₂ Furanyl Z₁: CH₂—CF₃ (3)CH₂ Pyrimidinyl NH—SO₂ Oxazolyl None CH₂ Pyrimidinyl NH—SO₂ Oxazolyl Z₁:F (2) CH₂ Pyrimidinyl NH—SO₂ Oxazolyl Z₁: F (3) CH₂ Pyrimidinyl NH—SO₂Oxazolyl Z₁: F (2) Z₂: F (3) CH₂ Pyrimidinyl NH—SO₂ Oxazolyl Z₁: Cl (2)CH₂ Pyrimidinyl NH—SO₂ Oxazolyl Z₁: Cl (3) CH₂ Pyrimidinyl NH—SO₂Oxazolyl Z₁: Cl (2) Z₂: Cl (3) CH₂ Pyrimidinyl NH—SO₂ Oxazolyl Z₁: F (2)Z₂: Cl (3) CH₂ Pyrimidinyl NH—SO₂ Oxazolyl Z₁: Cl (2) Z₂: F (3) CH₂Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CH₃ (2) CH₂ Pyrimidinyl NH—SO₂ OxazolylZ₁: CH₃ (3) CH₂ Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CH₂—CH₃ (2) CH₂Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CH₂—CH₃ (3) CH₂ Pyrimidinyl NH—SO₂Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂ Pyrimidinyl NH—SO₂ Oxazolyl Z₁:CH₂—CH₂—CH₃ or iPr (3) CH₂ Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CH₂F (2) CH₂Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CH₂F (3) CH₂ Pyrimidinyl NH—SO₂ OxazolylZ₁: CHF₂ (2) CH₂ Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CHF₂ (3) CH₂Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CF₃ (2) CH₂ Pyrimidinyl NH—SO₂ OxazolylZ₁: CF₃ (3) CH₂ Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CH₂—CH₂F (2) CH₂Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CH₂—CH₂F (3) CH₂ Pyrimidinyl NH—SO₂Oxazolyl Z₁: CH₂—CHF₂ (2) CH₂ Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CH₂—CHF₂(3) CH₂ Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CH₂—CF₃ (2) CH₂ PyrimidinylNH—SO₂ Oxazolyl Z₁: CH₂—CF₃ (3) CH₂ Pyrimidinyl NH—SO₂ Thiophenyl NoneCH₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁: F (2) CH₂ Pyrimidinyl NH—SO₂Thiophenyl Z₁: F (3) CH₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁: F (2) Z₂: F(3) CH₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁: Cl (2) CH₂ Pyrimidinyl NH—SO₂Thiophenyl Z₁: Cl (3) CH₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁: Cl (2) Z₂:Cl (3) CH₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁: F (2) Z₂: Cl (3) CH₂Pyrimidinyl NH—SO₂ Thiophenyl Z₁: Cl (2) Z₂: F (3) CH₂ PyrimidinylNH—SO₂ Thiophenyl Z₁: CH₃ (2) CH₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CH₃(3) CH₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₃ (2) CH₂ PyrimidinylNH—SO₂ Thiophenyl Z₁: CH₂—CH₃ (3) CH₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁:CH₂—CH₂—CH₃ or iPr (2) CH₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₂—CH₃or iPr (3) CH₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CH₂F (2) CH₂Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CH₂F (3) CH₂ Pyrimidinyl NH—SO₂Thiophenyl Z₁: CHF₂ (2) CH₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CHF₂ (3)CH₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CF₃ (2) CH₂ Pyrimidinyl NH—SO₂Thiophenyl Z₁: CF₃ (3) CH₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₂F(2) CH₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₂F (3) CH₂ PyrimidinylNH—SO₂ Thiophenyl Z₁: CH₂—CHF₂ (2) CH₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁:CH₂—CHF₂ (3) CH₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CH₂—CF₃ (2) CH₂Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CH₂—CF₃ (3) CH₂ Pyrimidinyl NH—SO₂Thiazolyl None CH₂ Pyrimidinyl NH—SO₂ Thiazolyl Z₁: F (2) CH₂Pyrimidinyl NH—SO₂ Thiazolyl Z₁: F (3) CH₂ Pyrimidinyl NH—SO₂ ThiazolylZ₁: F (2) Z₂: F (3) CH₂ Pyrimidinyl NH—SO₂ Thiazolyl Z₁: Cl (2) CH₂Pyrimidinyl NH—SO₂ Thiazolyl Z₁: Cl (3) CH₂ Pyrimidinyl NH—SO₂ ThiazolylZ₁: Cl (2) Z₂: Cl (3) CH₂ Pyrimidinyl NH—SO₂ Thiazolyl Z₁: F (2) Z₂: Cl(3) CH₂ Pyrimidinyl NH—SO₂ Thiazolyl Z₁: Cl (2) Z₂: F (3) CH₂Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CH₃ (2) CH₂ Pyrimidinyl NH—SO₂Thiazolyl Z₁: CH₃ (3) CH₂ Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₃ (2)CH₂ Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₃ (3) CH₂ Pyrimidinyl NH—SO₂Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂ Pyrimidinyl NH—SO₂ ThiazolylZ₁: CH₂—CH₂—CH₃ or iPr (3) CH₂ Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CH₂F (2)CH₂ Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CH₂F (3) CH₂ Pyrimidinyl NH—SO₂Thiazolyl Z₁: CHF₂ (2) CH₂ Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CHF₂ (3) CH₂Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CF₃ (2) CH₂ Pyrimidinyl NH—SO₂Thiazolyl Z₁: CF₃ (3) CH₂ Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₂F (2)CH₂ Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₂F (3) CH₂ Pyrimidinyl NH—SO₂Thiazolyl Z₁: CH₂—CHF₂ (2) CH₂ Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CH₂—CHF₂(3) CH₂ Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CH₂—CF₃ (2) CH₂ PyrimidinylNH—SO₂ Thiazolyl Z₁: CH₂—CF₃ (3) CH₂ Pyrazinyl NH—CH₂ Phenyl None CH₂Pyrazinyl NH—CH₂ Phenyl Z₁: F (para) CH₂ Pyrazinyl NH—CH₂ phenyl Z₁: F(meta) CH₂ Pyrazinyl NH—CH₂ phenyl Z₁: F (ortho) CH₂ Pyrazinyl NH—CH₂phenyl Z₁: F (para) Z₂: F (meta) CH₂ Pyrazinyl NH—CH₂ Phenyl Z₁: Cl(meta) CH₂ Pyrazinyl NH—CH₂ Phenyl Z₁: Cl (para) CH₂ Pyrazinyl NH—CH₂Phenyl Z₁: Cl (para) Z₂: Cl (meta) CH₂ Pyrazinyl NH—CH₂ Phenyl Z₁: F(para) Z₂: Cl (meta) CH₂ Pyrazinyl NH—CH₂ Phenyl Z₁: Cl (para) Z₂: F(meta) CH₂ Pyrazinyl NH—CH₂ Phenyl Z₁: CH₃ (para) CH₂ Pyrazinyl NH—CH₂Phenyl Z₁: CH₃ (meta) CH₂ Pyrazinyl NH—CH₂ Phenyl Z₁: CH₃ (ortho) CH₂Pyrazinyl NH—CH₂ Phenyl Z₁: CH₂—CH₃ (para) CH₂ Pyrazinyl NH—CH₂ PhenylZ₁: CH₂—CH₃ (meta) CH₂ Pyrazinyl NH—CH₂ Phenyl Z₁: CH₂—CH₃ (ortho) CH₂Pyrazinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CH₂ PyrazinylNH—CH₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CH₂ Pyrazinyl NH—CH₂ PhenylZ₁: CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyrazinyl NH—CH₂ Phenyl Z₁: CH₂F(para) CH₂ Pyrazinyl NH—CH₂ Phenyl Z₁: CH₂F (meta) CH₂ Pyrazinyl NH—CH₂Phenyl Z₁: CH₂F (ortho) CH₂ Pyrazinyl NH—CH₂ Phenyl Z₁: CHF₂ (para) CH₂Pyrazinyl NH—CH₂ Phenyl Z₁: CHF₂ (meta) CH₂ Pyrazinyl NH—CH₂ Phenyl Z₁:CHF₂ (ortho) CH₂ Pyrazinyl NH—CH₂ Phenyl Z₁: CF₃ (para) CH₂ PyrazinylNH—CH₂ Phenyl Z₁: CF₃ (meta) CH₂ Pyrazinyl NH—CH₂ Phenyl Z₁: CF₃ (ortho)CH₂ Pyrazinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂F (para) CH₂ Pyrazinyl NH—CH₂Phenyl Z₁: CH₂—CH₂F (meta) CH₂ Pyrazinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂F(ortho) CH₂ Pyrazinyl NH—CH₂ Phenyl Z₁: CH₂—CHF₂ (para) CH₂ PyrazinylNH—CH₂ Phenyl Z₁: CH₂—CHF₂ (meta) CH₂ Pyrazinyl NH—CH₂ Phenyl Z₁:CH₂—CHF₂ (ortho) CH₂ Pyrazinyl NH—CH₂ Phenyl Z₁: CH₂—CF₃ (para) CH₂Pyrazinyl NH—CH₂ Phenyl Z₁: CH₂—CF₃ (meta) CH₂ Pyrazinyl NH—CH₂ PhenylZ₁: CH₂—CF₃ (ortho) CH₂ Pyrazinyl NH—CH₂ Pyridinyl None CH₂ PyrazinylNH—CH₂ Pyridinyl Z₁: F (para) CH₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: F(meta) CH₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: F (ortho) CH₂ Pyrazinyl NH—CH₂Pyridinyl Z₁: F (para) Z₂: F (meta) CH₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁:Cl (meta) CH₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: Cl (para) CH₂ PyrazinylNH—CH₂ Pyridinyl Z₁: Cl (para) Z₂: Cl (meta) CH₂ Pyrazinyl NH—CH₂Pyridinyl Z₁: F (para) Z₂: Cl (meta) CH₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁:Cl (para) Z₂: F (meta) CH₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₃ (para) CH₂Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₃ (meta) CH₂ Pyrazinyl NH—CH₂ PyridinylZ₁: CH₃ (ortho) CH₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₃ (para) CH₂Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₃ (meta) CH₂ Pyrazinyl NH—CH₂Pyridinyl Z₁: CH₂—CH₃ (ortho) CH₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁:CH₂—CH₂—CH₃ or iPr (para) CH₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₂—CH₃or iPr (meta) CH₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr(ortho) CH₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂F (para) CH₂ PyrazinylNH—CH₂ Pyridinyl Z₁: CH₂F (meta) CH₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂F(ortho) CH₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: CHF₂ (para) CH₂ PyrazinylNH—CH₂ Pyridinyl Z₁: CHF₂ (meta) CH₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: CHF₂(ortho) CH₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: CF₃ (para) CH₂ PyrazinylNH—CH₂ Pyridinyl Z₁: CF₃ (meta) CH₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: CF₃(ortho) CH₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₂F (para) CH₂ PyrazinylNH—CH₂ Pyridinyl Z₁: CH₂—CH₂F (meta) CH₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁:CH₂—CH₂F (ortho) CH₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂—CHF₂ (para) CH₂Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂—CHF₂ (meta) CH₂ Pyrazinyl NH—CH₂Pyridinyl Z₁: CH₂—CHF₂ (ortho) CH₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁:CH₂—CF₃ (para) CH₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂—CF₃ (meta) CH₂Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂—CF₃ (ortho) CH₂ Pyrazinyl NH—CH₂Pyrimidinyl None CH₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: F (para) CH₂Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: F (meta) CH₂ Pyrazinyl NH—CH₂Pyrimidinyl Z₁: F (ortho) CH₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: F (para)Z₂: F (meta) CH₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: Cl (meta) CH₂Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: Cl (para) CH₂ Pyrazinyl NH—CH₂Pyrimidinyl Z₁: Cl (para) Z₂: Cl (meta) CH₂ Pyrazinyl NH—CH₂ PyrimidinylZ₁: F (para) Z₂: Cl (meta) CH₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: Cl(para) Z₁: F (meta) CH₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₃ (para) CH₂Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₃ (meta) CH₂ Pyrazinyl NH—CH₂Pyrimidinyl Z₁: CH₃ (ortho) CH₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₃(para) CH₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₃ (meta) CH₂ PyrazinylNH—CH₂ Pyrimidinyl Z₁: CH₂—CH₃ (ortho) CH₂ Pyrazinyl NH—CH₂ PyrimidinylZ₁: CH₂—CH₂—CH₃ or iPr (para) CH₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) CH₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₂F(para) CH₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₂F (meta) CH₂ PyrazinylNH—CH₂ Pyrimidinyl Z₁: CH₂F (ortho) CH₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁:CHF₂ (para) CH₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CHF₂ (meta) CH₂Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CHF₂ (ortho) CH₂ Pyrazinyl NH—CH₂Pyrimidinyl Z₁: CF₃ (para) CH₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CF₃(meta) CH₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CF₃ (ortho) CH₂ PyrazinylNH—CH₂ Pyrimidinyl Z₁: CH₂—CH₂F (para) CH₂ Pyrazinyl NH—CH₂ PyrimidinylZ₁: CH₂—CH₂F (meta) CH₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₂F(ortho) CH₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CHF₂ (para) CH₂Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CHF₂ (meta) CH₂ Pyrazinyl NH—CH₂Pyrimidinyl Z₁: CH₂—CHF₂ (ortho) CH₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁:CH₂—CF₃ (para) CH₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CF₃ (meta) CH₂Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CF₃ (ortho) CH₂ Pyrazinyl NH—CH₂Pyrazinyl None CH₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: F (para) CH₂ PyrazinylNH—CH₂ Pyrazinyl Z₁: F (meta) CH₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: F(ortho) CH₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: F (para) Z₂: F (meta) CH₂Pyrazinyl NH—CH₂ Pyrazinyl Z₁: Cl (meta) CH₂ Pyrazinyl NH—CH₂ PyrazinylZ₁: Cl (para) CH₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: Cl (para) Z₂: Cl (meta)CH₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: F (para) Z₂: Cl (meta) CH₂ PyrazinylNH—CH₂ Pyrazinyl Z₁: Cl (para) Z₂: F (meta) CH₂ Pyrazinyl NH—CH₂Pyrazinyl Z₁: CH₃ (para) CH₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₃ (meta)CH₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₃ (ortho) CH₂ Pyrazinyl NH—CH₂Pyrazinyl Z₁: CH₂—CH₃ (para) CH₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₃(meta) CH₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₃ (ortho) CH₂ PyrazinylNH—CH₂ Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CH₂ Pyrazinyl NH—CH₂Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CH₂ Pyrazinyl NH—CH₂ PyrazinylZ₁: CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂F(para) CH₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂F (meta) CH₂ PyrazinylNH—CH₂ Pyrazinyl Z₁: CH₂F (ortho) CH₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁:CHF₂ (para) CH₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CHF₂ (meta) CH₂ PyrazinylNH—CH₂ Pyrazinyl Z₁: CHF₂ (ortho) CH₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CF₃(para) CH₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CF₃ (meta) CH₂ PyrazinylNH—CH₂ Pyrazinyl Z₁: CF₃ (ortho) CH₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁:CH₂—CH₂F (para) CH₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₂F (meta) CH₂Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₂F (ortho) CH₂ Pyrazinyl NH—CH₂Pyrazinyl Z₁: CH₂—CHF₂ (para) CH₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁:CH₂—CHF₂ (meta) CH₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CHF₂ (ortho) CH₂Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CF₃ (para) CH₂ Pyrazinyl NH—CH₂Pyrazinyl Z₁: CH₂—CF₃ (meta) CH₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CF₃(ortho) CH₂ Pyrazinyl NH—CH₂ Pyrrolyl None CH₂ Pyrazinyl NH—CH₂ PyrrolylZ₁: F (2) CH₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: F (3) CH₂ Pyrazinyl NH—CH₂Pyrrolyl Z₁: F (2) Z₂: F (3) CH₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: Cl (2)CH₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: Cl (3) CH₂ Pyrazinyl NH—CH₂ PyrrolylZ₁: Cl (2) Z₂: Cl (3) CH₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: F (2) Z₂: Cl (3)CH₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: Cl (2) Z₂: F (3) CH₂ Pyrazinyl NH—CH₂Pyrrolyl Z₁: CH₃ (2) CH₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CH₃ (3) CH₂Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₃ (2) CH₂ Pyrazinyl NH—CH₂ PyrrolylZ₁: CH₂—CH₃ (3) CH₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (2)CH₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CH₂ PyrazinylNH—CH₂ Pyrrolyl Z₁: CH₂F (2) CH₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CH₂F (3)CH₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CHF₂ (2) CH₂ Pyrazinyl NH—CH₂ PyrrolylZ₁: CHF₂ (3) CH₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CF₃ (2) CH₂ PyrazinylNH—CH₂ Pyrrolyl Z₁: CF₃ (3) CH₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₂F(2) CH₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₂F (3) CH₂ Pyrazinyl NH—CH₂Pyrrolyl Z₁: CH₂—CHF₂ (2) CH₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CHF₂ (3)CH₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CF₃ (2) CH₂ Pyrazinyl NH—CH₂Pyrrolyl Z₁: CH₂—CF₃ (3) CH₂ Pyrazinyl NH—CH₂ Imidazolyl None CH₂Pyrazinyl NH—CH₂ Imidazolyl Z₁: F (2) CH₂ Pyrazinyl NH—CH₂ ImidazolylZ₁: F (3) CH₂ Pyrazinyl NH—CH₂ Imidazolyl Z₁: F (2) Z₂: F (3) CH₂Pyrazinyl NH—CH₂ Imidazolyl Z₁: Cl (2) CH₂ Pyrazinyl NH—CH₂ ImidazolylZ₁: Cl (3) CH₂ Pyrazinyl NH—CH₂ Imidazolyl Z₁: Cl (2) Z₂: Cl (3) CH₂Pyrazinyl NH—CH₂ Imidazolyl Z₁: F (2) Z₂: Cl (3) CH₂ Pyrazinyl NH—CH₂Imidazolyl Z₁: Cl (2) Z₂: F (3) CH₂ Pyrazinyl NH—CH₂ Imidazolyl Z₁: CH₃(2) CH₂ Pyrazinyl NH—CH₂ Imidazolyl Z₁: CH₃ (3) CH₂ Pyrazinyl NH—CH₂Imidazolyl Z₁: CH₂—CH₃ (2) CH₂ Pyrazinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₃(3) CH₂ Pyrazinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂Pyrazinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CH₂ PyrazinylNH—CH₂ Imidazolyl Z₁: CH₂F (2) CH₂ Pyrazinyl NH—CH₂ Imidazolyl Z₁: CH₂F(3) CH₂ Pyrazinyl NH—CH₂ Imidazolyl Z₁: CHF₂ (2) CH₂ Pyrazinyl NH—CH₂Imidazolyl Z₁: CHF₂ (3) CH₂ Pyrazinyl NH—CH₂ Imidazolyl Z₁: CF₃ (2) CH₂Pyrazinyl NH—CH₂ Imidazolyl Z₁: CF₃ (3) CH₂ Pyrazinyl NH—CH₂ ImidazolylZ₁: CH₂—CH₂F (2) CH₂ Pyrazinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₂F (3) CH₂Pyrazinyl NH—CH₂ Imidazolyl Z₁: CH₂—CHF₂ (2) CH₂ Pyrazinyl NH—CH₂Imidazolyl Z₁: CH₂—CHF₂ (3) CH₂ Pyrazinyl NH—CH₂ Imidazolyl Z₁: CH₂—CF₃(2) CH₂ Pyrazinyl NH—CH₂ Imidazolyl Z₁: CH₂—CF₃ (3) CH₂ Pyrazinyl NH—CH₂Furanyl None CH₂ Pyrazinyl NH—CH₂ Furanyl Z₁: F (2) CH₂ Pyrazinyl NH—CH₂Furanyl Z₁: F (3) CH₂ Pyrazinyl NH—CH₂ Furanyl Z₁: F (2) Z₂: F (3) CH₂Pyrazinyl NH—CH₂ Furanyl Z₁: Cl (2) CH₂ Pyrazinyl NH—CH₂ Furanyl Z₁: Cl(3) CH₂ Pyrazinyl NH—CH₂ Furanyl Z₁: Cl (2) Z₂: Cl (3) CH₂ PyrazinylNH—CH₂ Furanyl Z₁: F (2) Z₂: Cl (3) CH₂ Pyrazinyl NH—CH₂ Furanyl Z₁: Cl(2) Z₂: F (3) CH₂ Pyrazinyl NH—CH₂ Furanyl Z₁: CH₃ (2) CH₂ PyrazinylNH—CH₂ Furanyl Z₁: CH₃ (3) CH₂ Pyrazinyl NH—CH₂ Furanyl Z₁: CH₂—CH₃ (2)CH₂ Pyrazinyl NH—CH₂ Furanyl Z₁: CH₂—CH₃ (3) CH₂ Pyrazinyl NH—CH₂Furanyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂ Pyrazinyl NH—CH₂ Furanyl Z₁:CH₂—CH₂—CH₃ or iPr (3) CH₂ Pyrazinyl NH—CH₂ Furanyl Z₁: CH₂F (2) CH₂Pyrazinyl NH—CH₂ Furanyl Z₁: CH₂F (3) CH₂ Pyrazinyl NH—CH₂ Furanyl Z₁:CHF₂ (2) CH₂ Pyrazinyl NH—CH₂ Furanyl Z₁: CHF₂ (3) CH₂ Pyrazinyl NH—CH₂Furanyl Z₁: CF₃ (2) CH₂ Pyrazinyl NH—CH₂ Furanyl Z₁: CF₃ (3) CH₂Pyrazinyl NH—CH₂ Furanyl Z₁: CH₂—CH₂F (2) CH₂ pyrazinyl NH—CH₂ FuranylZ₁: CH₂—CH₂F (3) CH₂ Pyrazinyl NH—CH₂ Furanyl Z₁: CH₂—CHF₂ (2) CH₂Pyrazinyl NH—CH₂ Furanyl Z₁: CH₂—CHF₂ (3) CH₂ Pyrazinyl NH—CH₂ FuranylZ₁: CH₂—CF₃ (2) CH₂ Pyrazinyl NH—CH₂ Furanyl Z₁: CH₂—CF₃ (3) CH₂Pyrazinyl NH—CH₂ Oxazolyl None CH₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁: F (2)CH₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁: F (3) CH₂ Pyrazinyl NH—CH₂ OxazolylZ₁: F (2) Z₂: F (3) CH₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁: Cl (2) CH₂Pyrazinyl NH—CH₂ Oxazolyl Z₁: Cl (3) CH₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁:Cl (2) Z₂: Cl (3) CH₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁: F (2) Z₂: Cl (3) CH₂Pyrazinyl NH—CH₂ Oxazolyl Z₁: Cl (2) Z₂: F (3) CH₂ Pyrazinyl NH—CH₂Oxazolyl Z₁: CH₃ (2) CH₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁: CH₃ (3) CH₂Pyrazinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₃ (2) CH₂ Pyrazinyl NH—CH₂ OxazolylZ₁: CH₂—CH₃ (3) CH₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2)CH₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CH₂ PyrazinylNH—CH₂ Oxazolyl Z₁: CH₂F (2) CH₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁: CH₂F (3)CH₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁: CHF₂ (2) CH₂ Pyrazinyl NH—CH₂ OxazolylZ₁: CHF₂ (3) CH₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁: CF₃ (2) CH₂ PyrazinylNH—CH₂ Oxazolyl Z₁: CF₃ (3) CH₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₂F(2) CH₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₂F (3) CH₂ Pyrazinyl NH—CH₂Oxazolyl Z₁: CH₂—CHF₂ (2) CH₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁: CH₂—CHF₂ (3)CH₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁: CH₂—CF₃ (2) CH₂ Pyrazinyl NH—CH₂Oxazolyl Z₁: CH₂—CF₃ (3) CH₂ Pyrazinyl NH—CH₂ Thiophenyl None CH₂Pyrazinyl NH—CH₂ Thiophenyl Z₁: F (2) CH₂ Pyrazinyl NH—CH₂ ThiophenylZ₁: F (3) CH₂ Pyrazinyl NH—CH₂ Thiophenyl Z₁: F (2) Z₂: F (3) CH₂Pyrazinyl NH—CH₂ Thiophenyl Z₁: Cl (2) CH₂ Pyrazinyl NH—CH₂ ThiophenylZ₁: Cl (3) CH₂ Pyrazinyl NH—CH₂ Thiophenyl Z₁: Cl (2) Z₂: Cl (3) CH₂Pyrazinyl NH—CH₂ Thiophenyl Z₁: F (2) Z₂: Cl (3) CH₂ Pyrazinyl NH—CH₂Thiophenyl Z₁: Cl (2) Z₂: F (3) CH₂ Pyrazinyl NH—CH₂ Thiophenyl Z₁: CH₃(2) CH₂ Pyrazinyl NH—CH₂ Thiophenyl Z₁: CH₃ (3) CH₂ Pyrazinyl NH—CH₂Thiophenyl Z₁: CH₂—CH₃ (2) CH₂ Pyrazinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₃(3) CH₂ Pyrazinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂Pyrazinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CH₂ PyrazinylNH—CH₂ Thiophenyl Z₁: CH₂F (2) CH₂ Pyrazinyl NH—CH₂ Thiophenyl Z₁: CH₂F(3) CH₂ Pyrazinyl NH—CH₂ Thiophenyl Z₁: CHF₂ (2) CH₂ Pyrazinyl NH—CH₂Thiophenyl Z₁: CHF₂ (3) CH₂ Pyrazinyl NH—CH₂ Thiophenyl Z₁: CF₃ (2) CH₂Pyrazinyl NH—CH₂ Thiophenyl Z₁: CF₃ (3) CH₂ Pyrazinyl NH—CH₂ ThiophenylZ₁: CH₂—CH₂F (2) CH₂ Pyrazinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₂F (3) CH₂Pyrazinyl NH—CH₂ Thiophenyl Z₁: CH₂—CHF₂ (2) CH₂ Pyrazinyl NH—CH₂Thiophenyl Z₁: CH₂—CHF₂ (3) CH₂ Pyrazinyl NH—CH₂ Thiophenyl Z₁: CH₂—CF₃(2) CH₂ Pyrazinyl NH—CH₂ Thiophenyl Z₁: CH₂—CF₃ (3) CH₂ Pyrazinyl NH—CH₂Thiazolyl None CH₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁: F (2) CH₂ PyrazinylNH—CH₂ Thiazolyl Z₁: F (3) CH₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁: F (2) Z₂:F (3) CH₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁: Cl (2) CH₂ Pyrazinyl NH—CH₂Thiazolyl Z₁: Cl (3) CH₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁: Cl (2) Z₂: Cl(3) CH₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁: F (2) Z₂: Cl (3) CH₂ PyrazinylNH—CH₂ Thiazolyl Z₁: Cl (2) Z₂: F (3) CH₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁:CH₃ (2) CH₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁: CH₃ (3) CH₂ Pyrazinyl NH—CH₂Thiazolyl Z₁: CH₂—CH₃ (2) CH₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₃ (3)CH₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂ PyrazinylNH—CH₂ Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CH₂ Pyrazinyl NH—CH₂Thiazolyl Z₁: CH₂F (2) CH₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁: CH₂F (3) CH₂Pyrazinyl NH—CH₂ Thiazolyl Z₁: CHF₂ (2) CH₂ Pyrazinyl NH—CH₂ ThiazolylZ₁: CHF₂ (3) CH₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁: CF₃ (2) CH₂ PyrazinylNH—CH₂ Thiazolyl Z₁: CF₃ (3) CH₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₂F(2) CH₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₂F (3) CH₂ Pyrazinyl NH—CH₂Thiazolyl Z₁: CH₂—CHF₂ (2) CH₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁: CH₂—CHF₂(3) CH₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁: CH₂—CF₃ (2) CH₂ Pyrazinyl NH—CH₂Thiazolyl Z₁: CH₂—CF₃ (3) CH₂ Pyrazinyl NH—C(O) Phenyl None CH₂Pyrazinyl NH—C(O) Phenyl Z₁: F (para) CH₂ Pyrazinyl NH—C(O) phenyl Z₁: F(meta) CH₂ Pyrazinyl NH—C(O) phenyl Z₁: F (ortho) CH₂ Pyrazinyl NH—C(O)phenyl Z₁: F (para) Z₂: F (meta) CH₂ Pyrazinyl NH—C(O) Phenyl Z₁: Cl(meta) CH₂ Pyrazinyl NH—C(O) Phenyl Z₁: Cl (para) CH₂ Pyrazinyl NH—C(O)Phenyl Z₁: Cl (para) Z₂: Cl (meta) CH₂ Pyrazinyl NH—C(O) Phenyl Z₁: F(para) Z₂: Cl (meta) CH₂ Pyrazinyl NH—C(O) Phenyl Z₁: Cl (para) Z₂: F(meta) CH₂ Pyrazinyl NH—C(O) Phenyl Z₁: CH₃ (para) CH₂ Pyrazinyl NH—C(O)Phenyl Z₁: CH₃ (meta) CH₂ Pyrazinyl NH—C(O) Phenyl Z₁: CH₃ (ortho) CH₂Pyrazinyl NH—C(O) Phenyl Z₁: CH₂—CH₃ (para) CH₂ Pyrazinyl NH—C(O) PhenylZ₁: CH₂—CH₃ (meta) CH₂ Pyrazinyl NH—C(O) Phenyl Z₁: CH₂—CH₃ (ortho) CH₂Pyrazinyl NH—C(O) Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CH₂ PyrazinylNH—C(O) Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CH₂ Pyrazinyl NH—C(O)Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyrazinyl NH—C(O) Phenyl Z₁:CH₂F (para) CH₂ Pyrazinyl NH—C(O) Phenyl Z₁: CH₂F (meta) CH₂ PyrazinylNH—C(O) Phenyl Z₁: CH₂F (ortho) CH₂ Pyrazinyl NH—C(O) Phenyl Z₁: CHF₂(para) CH₂ Pyrazinyl NH—C(O) Phenyl Z₁: CHF₂ (meta) CH₂ PyrazinylNH—C(O) Phenyl Z₁: CHF₂ (ortho) CH₂ Pyrazinyl NH—C(O) Phenyl Z₁: CF₃(para) CH₂ Pyrazinyl NH—C(O) Phenyl Z₁: CF₃ (meta) CH₂ Pyrazinyl NH—C(O)Phenyl Z₁: CF₃ (ortho) CH₂ Pyrazinyl NH—C(O) Phenyl Z₁: CH₂—CH₂F (para)CH₂ Pyrazinyl NH—C(O) Phenyl Z₁: CH₂—CH₂F (meta) CH₂ Pyrazinyl NH—C(O)Phenyl Z₁: CH₂—CH₂F (ortho) CH₂ Pyrazinyl NH—C(O) Phenyl Z₁: CH₂—CHF₂(para) CH₂ Pyrazinyl NH—C(O) Phenyl Z₁: CH₂—CHF₂ (meta) CH₂ PyrazinylNH—C(O) Phenyl Z₁: CH₂—CHF₂ (ortho) CH₂ Pyrazinyl NH—C(O) Phenyl Z₁:CH₂—CF₃ (para) CH₂ Pyrazinyl NH—C(O) Phenyl Z₁: CH₂—CF₃ (meta) CH₂Pyrazinyl NH—C(O) Phenyl Z₁: CH₂—CF₃ (ortho) CH₂ Pyrazinyl NH—C(O)Pyridinyl None CH₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: F (para) CH₂Pyrazinyl NH—C(O) Pyridinyl Z₁: F (meta) CH₂ Pyrazinyl NH—C(O) PyridinylZ₁: F (ortho) CH₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: F (para) Z₂: F (meta)CH₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: Cl (meta) CH₂ Pyrazinyl NH—C(O)Pyridinyl Z₁: Cl (para) CH₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: Cl (para)Z₂: Cl (meta) CH₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: F (para) Z₁: Cl (meta)CH₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: Cl (para) Z₂: F (meta) CH₂ PyrazinylNH—C(O) Pyridinyl Z₁: CH₃ (para) CH₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₃(meta) CH₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₃ (ortho) CH₂ PyrazinylNH—C(O) Pyridinyl Z₁: CH₂—CH₃ (para) CH₂ Pyrazinyl NH—C(O) Pyridinyl Z₁:CH₂—CH₃ (meta) CH₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₃ (ortho) CH₂Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CH₂ PyrazinylNH—C(O) Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CH₂ Pyrazinyl NH—C(O)Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyrazinyl NH—C(O) PyridinylZ₁: CH₂F (para) CH₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₂F (meta) CH₂Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₂F (ortho) CH₂ Pyrazinyl NH—C(O)Pyridinyl Z₁: CHF₂ (para) CH₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: CHF₂(meta) CH₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: CHF₂ (ortho) CH₂ PyrazinylNH—C(O) Pyridinyl Z₁: CF₃ (para) CH₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: CF₃(meta) CH₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: CF₃ (ortho) CH₂ PyrazinylNH—C(O) Pyridinyl Z₁: CH₂—CH₂F (para) CH₂ Pyrazinyl NH—C(O) PyridinylZ₁: CH₂—CH₂F (meta) CH₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₂F (ortho)CH₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₂—CHF₂ (para) CH₂ PyrazinylNH—C(O) Pyridinyl Z₁: CH₂—CHF₂ (meta) CH₂ Pyrazinyl NH—C(O) PyridinylZ₁: CH₂—CHF₂ (ortho) CH₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₂—CF₃ (para)CH₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₂—CF₃ (meta) CH₂ Pyrazinyl NH—C(O)Pyridinyl Z₁: CH₂—CF₃ (ortho) CH₂ Pyrazinyl NH—C(O) Pyrimidinyl None CH₂Pyrazinyl NH—C(O) Pyrimidinyl Z₁: F (para) CH₂ Pyrazinyl NH—C(O)Pyrimidinyl Z₁: F (meta) CH₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: F (ortho)CH₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: F (para) Z₂: F (meta) CH₂Pyrazinyl NH—C(O) Pyrimidinyl Z₁: Cl (meta) CH₂ Pyrazinyl NH—C(O)Pyrimidinyl Z₁: Cl (para) CH₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: Cl(para) Z₂: Cl (meta) CH₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: F (para) Z₂:Cl (meta) CH₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: Cl (para) Z₂: F (meta)CH₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₃ (para) CH₂ Pyrazinyl NH—C(O)Pyrimidinyl Z₁: CH₃ (meta) CH₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₃(ortho) CH₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CH₃ (para) CH₂Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CH₃ (meta) CH₂ Pyrazinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CH₃ (ortho) CH₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (para) CH₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) CH₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₂F(para) CH₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₂F (meta) CH₂ PyrazinylNH—C(O) Pyrimidinyl Z₁: CH₂F (ortho) CH₂ Pyrazinyl NH—C(O) PyrimidinylZ₁: CHF₂ (para) CH₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CHF₂ (meta) CH₂Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CHF₂ (ortho) CH₂ Pyrazinyl NH—C(O)Pyrimidinyl Z₁: CF₃ (para) CH₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CF₃(meta) CH₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CF₃ (ortho) CH₂ PyrazinylNH—C(O) Pyrimidinyl Z₁: CH₂—CH₂F (para) CH₂ Pyrazinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CH₂F (meta) CH₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CH₂F (ortho) CH₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CHF₂ (para)CH₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CHF₂ (meta) CH₂ PyrazinylNH—C(O) Pyrimidinyl Z₁: CH₂—CHF₂ (ortho) CH₂ Pyrazinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CF₃ (para) CH₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CF₃ (meta) CH₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CF₃ (ortho) CH₂Pyrazinyl NH—C(O) Pyrazinyl None CH₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: F(para) CH₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: F (meta) CH₂ PyrazinylNH—C(O) Pyrazinyl Z₁: F (ortho) CH₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: F(para) Z₂: F (meta) CH₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: Cl (meta) CH₂Pyrazinyl NH—C(O) Pyrazinyl Z₁: Cl (para) CH₂ Pyrazinyl NH—C(O)Pyrazinyl Z₁: Cl (para) Z₂: Cl (meta) CH₂ Pyrazinyl NH—C(O) PyrazinylZ₁: F (para) Z₂: Cl (meta) CH₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: Cl (para)Z₂: F (meta) CH₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: CH₃ (para) CH₂Pyrazinyl NH—C(O) Pyrazinyl Z₁: CH₃ (meta) CH₂ Pyrazinyl NH—C(O)Pyrazinyl Z₁: CH₃ (ortho) CH₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: CH₂—CH₃(para) CH₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: CH₂—CH₃ (meta) CH₂ PyrazinylNH—C(O) Pyrazinyl Z₁: CH₂—CH₃ (ortho) CH₂ Pyrazinyl NH—C(O) PyrazinylZ₁: CH₂—CH₂—CH₃ or iPr (para) CH₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) CH₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: CH₂F(para) CH₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: CH₂F (meta) CH₂ PyrazinylNH—C(O) Pyrazinyl Z₁: CH₂F (ortho) CH₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁:CHF₂ (para) CH₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: CHF₂ (meta) CH₂Pyrazinyl NH—C(O) Pyrazinyl Z₁: CHF₂ (ortho) CH₂ Pyrazinyl NH—C(O)Pyrazinyl Z₁: CF₃ (para) CH₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: CF₃ (meta)CH₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: CF₃ (ortho) CH₂ Pyrazinyl NH—C(O)Pyrazinyl Z₁: CH₂—CH₂F (para) CH₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁:CH₂—CH₂F (meta) CH₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: CH₂—CH₂F (ortho) CH₂Pyrazinyl NH—C(O) Pyrazinyl Z₁: CH₂—CHF₂ (para) CH₂ Pyrazinyl NH—C(O)Pyrazinyl Z₁: CH₂—CHF₂ (meta) CH₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁:CH₂—CHF₂ (ortho) CH₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: CH₂—CF₃ (para) CH₂Pyrazinyl NH—C(O) Pyrazinyl Z₁: CH₂—CF₃ (meta) CH₂ Pyrazinyl NH—C(O)Pyrazinyl Z₁: CH₂—CF₃ (ortho) CH₂ Pyrazinyl NH—C(O) Pyrrolyl None CH₂Pyrazinyl NH—C(O) Pyrrolyl Z₁: F (2) CH₂ Pyrazinyl NH—C(O) Pyrrolyl Z₁:F (3) CH₂ Pyrazinyl NH—C(O) Pyrrolyl Z₁: F (2) Z₂: F (3) CH₂ PyrazinylNH—C(O) Pyrrolyl Z₁: Cl (2) CH₂ Pyrazinyl NH—C(O) Pyrrolyl Z₁: Cl (3)CH₂ Pyrazinyl NH—C(O) Pyrrolyl Z₁: Cl (2) Z₂: Cl (3) CH₂ PyrazinylNH—C(O) Pyrrolyl Z₁: F (2) Z₂: Cl (3) CH₂ Pyrazinyl NH—C(O) Pyrrolyl Z₁:Cl (2) Z₂: F (3) CH₂ Pyrazinyl NH—C(O) Pyrrolyl Z₁: CH₃ (2) CH₂Pyrazinyl NH—C(O) Pyrrolyl Z₁: CH₃ (3) CH₂ Pyrazinyl NH—C(O) PyrrolylZ₁: CH₂—CH₃ (2) CH₂ Pyrazinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₃ (3) CH₂Pyrazinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂ PyrazinylNH—C(O) Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CH₂ Pyrazinyl NH—C(O)Pyrrolyl Z₁: CH₂F (2) CH₂ Pyrazinyl NH—C(O) Pyrrolyl Z₁: CH₂F (3) CH₂Pyrazinyl NH—C(O) Pyrrolyl Z₁: CHF₂ (2) CH₂ Pyrazinyl NH—C(O) PyrrolylZ₁: CHF₂ (3) CH₂ Pyrazinyl NH—C(O) Pyrrolyl Z₁: CF₃ (2) CH₂ PyrazinylNH—C(O) Pyrrolyl Z₁: CF₃ (3) CH₂ Pyrazinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₂F(2) CH₂ Pyrazinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₂F (3) CH₂ PyrazinylNH—C(O) Pyrrolyl Z₁: CH₂—CHF₂ (2) CH₂ Pyrazinyl NH—C(O) Pyrrolyl Z₁:CH₂—CHF₂ (3) CH₂ Pyrazinyl NH—C(O) Pyrrolyl Z₁: CH₂—CF₃ (2) CH₂Pyrazinyl NH—C(O) Pyrrolyl Z₁: CH₂—CF₃ (3) CH₂ Pyrazinyl NH—C(O)Imidazolyl None CH₂ Pyrazinyl NH—C(O) Imidazolyl Z₁: F (2) CH₂ PyrazinylNH—C(O) Imidazolyl Z₁: F (3) CH₂ Pyrazinyl NH—C(O) Imidazolyl Z₁: F (2)Z₂: F (3) CH₂ Pyrazinyl NH—C(O) Imidazolyl Z₁: Cl (2) CH₂ PyrazinylNH—C(O) Imidazolyl Z₁: Cl (3) CH₂ Pyrazinyl NH—C(O) Imidazolyl Z₁: Cl(2) Z₂: Cl (3) CH₂ Pyrazinyl NH—C(O) Imidazolyl Z₁: F (2) Z₂: Cl (3) CH₂Pyrazinyl NH—C(O) Imidazolyl Z₁: Cl (2) Z₂: F (3) CH₂ Pyrazinyl NH—C(O)Imidazolyl Z₁: CH₃ (2) CH₂ Pyrazinyl NH—C(O) Imidazolyl Z₁: CH₃ (3) CH₂Pyrazinyl NH—C(O) Imidazolyl Z₁: CH₂—CH₃ (2) CH₂ Pyrazinyl NH—C(O)Imidazolyl Z₁: CH₂—CH₃ (3) CH₂ Pyrazinyl NH—C(O) Imidazolyl Z₁:CH₂—CH₂—CH₃ or iPr (2) CH₂ Pyrazinyl NH—C(O) Imidazolyl Z₁: CH₂—CH₂—CH₃or iPr (3) CH₂ Pyrazinyl NH—C(O) Imidazolyl Z₁: CH₂F (2) CH₂ PyrazinylNH—C(O) Imidazolyl Z₁: CH₂F (3) CH₂ Pyrazinyl NH—C(O) Imidazolyl Z₁:CHF₂ (2) CH₂ Pyrazinyl NH—C(O) Imidazolyl Z₁: CHF₂ (3) CH₂ PyrazinylNH—C(O) Imidazolyl Z₁: CF₃ (2) CH₂ Pyrazinyl NH—C(O) Imidazolyl Z₁: CF₃(3) CH₂ Pyrazinyl NH—C(O) Imidazolyl Z₁: CH₂—CH₂F (2) CH₂ PyrazinylNH—C(O) Imidazolyl Z₁: CH₂—CH₂F (3) CH₂ Pyrazinyl NH—C(O) Imidazolyl Z₁:CH₂—CHF₂ (2) CH₂ Pyrazinyl NH—C(O) Imidazolyl Z₁: CH₂—CHF₂ (3) CH₂Pyrazinyl NH—C(O) Imidazolyl Z₁: CH₂—CF₃ (2) CH₂ Pyrazinyl NH—C(O)Imidazolyl Z₁: CH₂—CF₃ (3) CH₂ Pyrazinyl NH—C(O) Furanyl None CH₂Pyrazinyl NH—C(O) Furanyl Z₁: F (2) CH₂ Pyrazinyl NH—C(O) Furanyl Z₁: F(3) CH₂ Pyrazinyl NH—C(O) Furanyl Z₁: F (2) Z₂: F (3) CH₂ PyrazinylNH—C(O) Furanyl Z₁: Cl (2) CH₂ Pyrazinyl NH—C(O) Furanyl Z₁: Cl (3) CH₂Pyrazinyl NH—C(O) Furanyl Z₁: Cl (2) Z₂: Cl (3) CH₂ Pyrazinyl NH—C(O)Furanyl Z₁: F (2) Z₂: Cl (3) CH₂ Pyrazinyl NH—C(O) Furanyl Z₁: Cl (2)Z₂: F (3) CH₂ Pyrazinyl NH—C(O) Furanyl Z₁: CH₃ (2) CH₂ PyrazinylNH—C(O) Furanyl Z₁: CH₃ (3) CH₂ Pyrazinyl NH—C(O) Furanyl Z₁: CH₂—CH₃(2) CH₂ Pyrazinyl NH—C(O) Furanyl Z₁: CH₂—CH₃ (3) CH₂ Pyrazinyl NH—C(O)Furanyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂ Pyrazinyl NH—C(O) Furanyl Z₁:CH₂—CH₂—CH₃ or iPr (3) CH₂ Pyrazinyl NH—C(O) Furanyl Z₁: CH₂F (2) CH₂Pyrazinyl NH—C(O) Furanyl Z₁: CH₂F (3) CH₂ Pyrazinyl NH—C(O) Furanyl Z₁:CHF₂ (2) CH₂ Pyrazinyl NH—C(O) Furanyl Z₁: CHF₂ (3) CH₂ PyrazinylNH—C(O) Furanyl Z₁: CF₃ (2) CH₂ Pyrazinyl NH—C(O) Furanyl Z₁: CF₃ (3)CH₂ Pyrazinyl NH—C(O) Furanyl Z₁: CH₂—CH₂F (2) CH₂ Pyrazinyl NH—C(O)Furanyl Z₁: CH₂—CH₂F (3) CH₂ Pyrazinyl NH—C(O) Furanyl Z₁: CH₂—CHF₂ (2)CH₂ Pyrazinyl NH—C(O) Furanyl Z₁: CH₂—CHF₂ (3) CH₂ Pyrazinyl NH—C(O)Furanyl Z₁: CH₂—CF₃ (2) CH₂ Pyrazinyl NH—C(O) Furanyl Z₁: CH₂—CF₃ (3)CH₂ Pyrazinyl NH—C(O) Oxazolyl None CH₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: F(2) CH₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: F (3) CH₂ Pyrazinyl NH—C(O)Oxazolyl Z₁: F (2) Z₂: F (3) CH₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: Cl (2)CH₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: Cl (3) CH₂ Pyrazinyl NH—C(O) OxazolylZ₁: Cl (2) Z₂: Cl (3) CH₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: F (2) Z₂: Cl(3) CH₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: Cl (2) Z₂: F (3) CH₂ PyrazinylNH—C(O) Oxazolyl Z₁: CH₃ (2) CH₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: CH₃ (3)CH₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₃ (2) CH₂ Pyrazinyl NH—C(O)Oxazolyl Z₁: CH₂—CH₃ (3) CH₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₂—CH₃or iPr (2) CH₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CH₂Pyrazinyl NH—C(O) Oxazolyl Z₁: CH₂F (2) CH₂ Pyrazinyl NH—C(O) OxazolylZ₁: CH₂F (3) CH₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: CHF₂ (2) CH₂ PyrazinylNH—C(O) Oxazolyl Z₁: CHF₂ (3) CH₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: CF₃ (2)CH₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: CF₃ (3) CH₂ Pyrazinyl NH—C(O)Oxazolyl Z₁: CH₂—CH₂F (2) CH₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₂F(3) CH₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: CH₂—CHF₂ (2) CH₂ PyrazinylNH—C(O) Oxazolyl Z₁: CH₂—CHF₂ (3) CH₂ Pyrazinyl NH—C(O) Oxazolyl Z₁:CH₂—CF₃ (2) CH₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: CH₂—CF₃ (3) CH₂ PyrazinylNH—C(O) Thiophenyl None CH₂ Pyrazinyl NH—C(O) Thiophenyl Z₁: F (2) CH₂Pyrazinyl NH—C(O) Thiophenyl Z₁: F (3) CH₂ Pyrazinyl NH—C(O) ThiophenylZ₁: F (2) Z₂: F (3) CH₂ Pyrazinyl NH—C(O) Thiophenyl Z₁: Cl (2) CH₂Pyrazinyl NH—C(O) Thiophenyl Z₁: Cl (3) CH₂ Pyrazinyl NH—C(O) ThiophenylZ₁: Cl (2) Z₂: Cl (3) CH₂ Pyrazinyl NH—C(O) Thiophenyl Z₁: F (2) Z₂: Cl(3) CH₂ Pyrazinyl NH—C(O) Thiophenyl Z₁: Cl (2) Z₂: F (3) CH₂ PyrazinylNH—C(O) Thiophenyl Z₁: CH₃ (2) CH₂ Pyrazinyl NH—C(O) Thiophenyl Z₁: CH₃(3) CH₂ Pyrazinyl NH—C(O) Thiophenyl Z₁: CH₂—CH₃ (2) CH₂ PyrazinylNH—C(O) Thiophenyl Z₁: CH₂—CH₃ (3) CH₂ Pyrazinyl NH—C(O) Thiophenyl Z₁:CH₂—CH₂—CH₃ or iPr (2) CH₂ Pyrazinyl NH—C(O) Thiophenyl Z₁: CH₂—CH₂—CH₃or iPr (3) CH₂ Pyrazinyl NH—C(O) Thiophenyl Z₁: CH₂F (2) CH₂ PyrazinylNH—C(O) Thiophenyl Z₁: CH₂F (3) CH₂ Pyrazinyl NH—C(O) Thiophenyl Z₁:CHF₂ (2) CH₂ Pyrazinyl NH—C(O) Thiophenyl Z₁: CHF₂ (3) CH₂ PyrazinylNH—C(O) Thiophenyl Z₁: CF₃ (2) CH₂ Pyrazinyl NH—C(O) Thiophenyl Z₁: CF₃(3) CH₂ Pyrazinyl NH—C(O) Thiophenyl Z₁: CH₂—CH₂F (2) CH₂ PyrazinylNH—C(O) Thiophenyl Z₁: CH₂—CH₂F (3) CH₂ Pyrazinyl NH—C(O) Thiophenyl Z₁:CH₂—CHF₂ (2) CH₂ Pyrazinyl NH—C(O) Thiophenyl Z₁: CH₂—CHF₂ (3) CH₂Pyrazinyl NH—C(O) Thiophenyl Z₁: CH₂—CF₃ (2) CH₂ Pyrazinyl NH—C(O)Thiophenyl Z₁: CH₂—CF₃ (3) CH₂ Pyrazinyl NH—C(O) Thiazolyl None CH₂Pyrazinyl NH—C(O) Thiazolyl Z₁: F (2) CH₂ Pyrazinyl NH—C(O) ThiazolylZ₁: F (3) CH₂ Pyrazinyl NH—C(O) Thiazolyl Z₁: F (2) Z₂: F (3) CH₂Pyrazinyl NH—C(O) Thiazolyl Z₁: Cl (2) CH₂ Pyrazinyl NH—C(O) ThiazolylZ₁: Cl (3) CH₂ Pyrazinyl NH—C(O) Thiazolyl Z₁: Cl (2) Z₂: Cl (3) CH₂Pyrazinyl NH—C(O) Thiazolyl Z₁: F (2) Z₂: Cl (3) CH₂ Pyrazinyl NH—C(O)Thiazolyl Z₁: Cl (2) Z₂: F (3) CH₂ Pyrazinyl NH—C(O) Thiazolyl Z₁: CH₃(2) CH₂ Pyrazinyl NH—C(O) Thiazolyl Z₁: CH₃ (3) CH₂ Pyrazinyl NH—C(O)Thiazolyl Z₁: CH₂—CH₃ (2) CH₂ Pyrazinyl NH—C(O) Thiazolyl Z₁: CH₂—CH₃(3) CH₂ Pyrazinyl NH—C(O) Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂Pyrazinyl NH—C(O) Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CH₂ PyrazinylNH—C(O) Thiazolyl Z₁: CH₂F (2) CH₂ Pyrazinyl NH—C(O) Thiazolyl Z₁: CH₂F(3) CH₂ Pyrazinyl NH—C(O) Thiazolyl Z₁: CHF₂ (2) CH₂ Pyrazinyl NH—C(O)Thiazolyl Z₁: CHF₂ (3) CH₂ Pyrazinyl NH—C(O) Thiazolyl Z₁: CF₃ (2) CH₂Pyrazinyl NH—C(O) Thiazolyl Z₁: CF₃ (3) CH₂ Pyrazinyl NH—C(O) ThiazolylZ₁: CH₂—CH₂F (2) CH₂ Pyrazinyl NH—C(O) Thiazolyl Z₁: CH₂—CH₂F (3) CH₂Pyrazinyl NH—C(O) Thiazolyl Z₁: CH₂—CHF₂ (2) CH₂ Pyrazinyl NH—C(O)Thiazolyl Z₁: CH₂—CHF₂ (3) CH₂ Pyrazinyl NH—C(O) Thiazolyl Z₁: CH₂—CF₃(2) CH₂ Pyrazinyl NH—C(O) Thiazolyl Z₁: CH₂—CF₃ (3) CH₂ Pyrazinyl NH—SO₂Phenyl None CH₂ Pyrazinyl NH—SO₂ Phenyl Z₁: F (para) CH₂ PyrazinylNH—SO₂ phenyl Z₁: F (meta) CH₂ Pyrazinyl NH—SO₂ phenyl Z₁: F (ortho) CH₂Pyrazinyl NH—SO₂ phenyl Z₁: F (para) Z₂: F (meta) CH₂ Pyrazinyl NH—SO₂Phenyl Z₁: Cl (meta) CH₂ Pyrazinyl NH—SO₂ Phenyl Z₁: Cl (para) CH₂Pyrazinyl NH—SO₂ Phenyl Z₁: Cl (para) Z₂: Cl (meta) CH₂ Pyrazinyl NH—SO₂Phenyl Z₁: F (para) Z₂: Cl (meta) CH₂ Pyrazinyl NH—SO₂ Phenyl Z₁: Cl(para) Z₂: F (meta) CH₂ Pyrazinyl NH—SO₂ Phenyl Z₁: CH₃ (para) CH₂Pyrazinyl NH—SO₂ Phenyl Z₁: CH₃ (meta) CH₂ Pyrazinyl NH—SO₂ Phenyl Z₁:CH₃ (ortho) CH₂ Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂—CH₃ (para) CH₂ PyrazinylNH—SO₂ Phenyl Z₁: CH₂—CH₃ (meta) CH₂ Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂—CH₃(ortho) CH₂ Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CH₂Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CH₂ PyrazinylNH—SO₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyrazinyl NH—SO₂ PhenylZ₁: CH₂F (para) CH₂ Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂F (meta) CH₂Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂F (ortho) CH₂ Pyrazinyl NH—SO₂ Phenyl Z₁:CHF₂ (para) CH₂ Pyrazinyl NH—SO₂ Phenyl Z₁: CHF₂ (meta) CH₂ PyrazinylNH—SO₂ Phenyl Z₁: CHF₂ (ortho) CH₂ Pyrazinyl NH—SO₂ Phenyl Z₁: CF₃(para) CH₂ Pyrazinyl NH—SO₂ Phenyl Z₁: CF₃ (meta) CH₂ Pyrazinyl NH—SO₂Phenyl Z₁: CF₃ (ortho) CH₂ Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂F (para)CH₂ Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂F (meta) CH₂ Pyrazinyl NH—SO₂Phenyl Z₁: CH₂—CH₂F (ortho) CH₂ Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂—CHF₂(para) CH₂ Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂—CHF₂ (meta) CH₂ PyrazinylNH—SO₂ Phenyl Z₁: CH₂—CHF₂ (ortho) CH₂ Pyrazinyl NH—SO₂ Phenyl Z₁:CH₂—CF₃ (para) CH₂ Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂—CF₃ (meta) CH₂Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂—CF₃ (ortho) CH₂ Pyrazinyl NH—SO₂Pyridinyl None CH₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: F (para) CH₂ PyrazinylNH—SO₂ Pyridinyl Z₁: F (meta) CH₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: F(ortho) CH₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: F (para) Z₂: F (meta) CH₂Pyrazinyl NH—SO₂ Pyridinyl Z₁: Cl (meta) CH₂ Pyrazinyl NH—SO₂ PyridinylZ₁: Cl (para) CH₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: Cl (para) Z₂: Cl (meta)CH₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: F (para) Z₂: Cl (meta) CH₂ PyrazinylNH—SO₂ Pyridinyl Z₁: Cl (para) Z₂: F (meta) CH₂ Pyrazinyl NH—SO₂Pyridinyl Z₁: CH₃ (para) CH₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₃ (meta)CH₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₃ (ortho) CH₂ Pyrazinyl NH—SO₂Pyridinyl Z₁: CH₂—CH₃ (para) CH₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₃(meta) CH₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₃ (ortho) CH₂ PyrazinylNH—SO₂ Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CH₂ Pyrazinyl NH—SO₂Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CH₂ Pyrazinyl NH—SO₂ PyridinylZ₁: CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₂F(para) CH₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₂F (meta) CH₂ PyrazinylNH—SO₂ Pyridinyl Z₁: CH₂F (ortho) CH₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁:CHF₂ (para) CH₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: CHF₂ (meta) CH₂ PyrazinylNH—SO₂ Pyridinyl Z₁: CHF₂ (ortho) CH₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: CF₃(para) CH₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: CF₃ (meta) CH₂ PyrazinylNH—SO₂ Pyridinyl Z₁: CF₃ (ortho) CH₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁:CH₂—CH₂F (para) CH₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₂F (meta) CH₂Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₂F (ortho) CH₂ Pyrazinyl NH—SO₂Pyridinyl Z₁: CH₂—CHF₂ (para) CH₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁:CH₂—CHF₂ (meta) CH₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₂—CHF₂ (ortho) CH₂Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₂—CF₃ (para) CH₂ Pyrazinyl NH—SO₂Pyridinyl Z₁: CH₂—CF₃ (meta) CH₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₂—CF₃(ortho) CH₂ Pyrazinyl NH—SO₂ Pyrimidinyl None CH₂ Pyrazinyl NH—SO₂Pyrimidinyl Z₁: F (para) CH₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: F (meta)CH₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: F (ortho) CH₂ Pyrazinyl NH—SO₂Pyrimidinyl Z₁: F (para) Z₂: F (meta) CH₂ Pyrazinyl NH—SO₂ PyrimidinylZ₁: Cl (meta) CH₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: Cl (para) CH₂Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: Cl (para) Z₂: Cl (meta) CH₂ PyrazinylNH—SO₂ Pyrimidinyl Z₁: F (para) Z₂: Cl (meta) CH₂ Pyrazinyl NH—SO₂Pyrimidinyl Z₁: Cl (para) Z₂: F (meta) CH₂ Pyrazinyl NH—SO₂ PyrimidinylZ₁: CH₃ (para) CH₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₃ (meta) CH₂Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₃ (ortho) CH₂ Pyrazinyl NH—SO₂Pyrimidinyl Z₁: CH₂—CH₃ (para) CH₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁:CH₂—CH₃ (meta) CH₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₃ (ortho) CH₂Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CH₂ PyrazinylNH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CH₂ Pyrazinyl NH—SO₂Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyrazinyl NH—SO₂Pyrimidinyl Z₁: CH₂F (para) CH₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₂F(meta) CH₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₂F (ortho) CH₂ PyrazinylNH—SO₂ Pyrimidinyl Z₁: CHF₂ (para) CH₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁:CHF₂ (meta) CH₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CHF₂ (ortho) CH₂Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CF₃ (para) CH₂ Pyrazinyl NH—SO₂Pyrimidinyl Z₁: CF₃ (meta) CH₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CF₃(ortho) CH₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂F (para) CH₂Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂F (meta) CH₂ Pyrazinyl NH—SO₂Pyrimidinyl Z₁: CH₂—CH₂F (ortho) CH₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁:CH₂—CHF₂ (para) CH₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CHF₂ (meta) CH₂Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CHF₂ (ortho) CH₂ Pyrazinyl NH—SO₂Pyrimidinyl Z₁: CH₂—CF₃ (para) CH₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁:CH₂—CF₃ (meta) CH₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CF₃ (ortho) CH₂Pyrazinyl NH—SO₂ Pyrazinyl None CH₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: F(para) CH₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: F (meta) CH₂ Pyrazinyl NH—SO₂Pyrazinyl Z₁: F (ortho) CH₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: F (para) Z₂:F (meta) CH₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: Cl (meta) CH₂ PyrazinylNH—SO₂ Pyrazinyl Z₁: Cl (para) CH₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: Cl(para) Z₂: Cl (meta) CH₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: F (para) Z₂: Cl(meta) CH₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: Cl (para) Z₂: F (meta) CH₂Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₃ (para) CH₂ Pyrazinyl NH—SO₂ PyrazinylZ₁: CH₃ (meta) CH₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₃ (ortho) CH₂Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₃ (para) CH₂ Pyrazinyl NH—SO₂Pyrazinyl Z₁: CH₂—CH₃ (meta) CH₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₃(ortho) CH₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CH₂Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CH₂ PyrazinylNH—SO₂ Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) CH₂ Pyrazinyl NH—SO₂Pyrazinyl Z₁: CH₂F (para) CH₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₂F (meta)CH₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₂F (ortho) CH₂ Pyrazinyl NH—SO₂Pyrazinyl Z₁: CHF₂ (para) CH₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CHF₂ (meta)CH₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CHF₂ (ortho) CH₂ Pyrazinyl NH—SO₂Pyrazinyl Z₁: CF₃ (para) CH₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CF₃ (meta)CH₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CF₃ (ortho) CH₂ Pyrazinyl NH—SO₂Pyrazinyl Z₁: CH₂—CH₂F (para) CH₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁:CH₂—CH₂F (meta) CH₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₂F (ortho) CH₂Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CHF₂ (para) CH₂ Pyrazinyl NH—SO₂Pyrazinyl Z₁: CH₂—CHF₂ (meta) CH₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁:CH₂—CHF₂ (ortho) CH₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CF₃ (para) CH₂Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CF₃ (meta) CH₂ Pyrazinyl NH—SO₂Pyrazinyl Z₁: CH₂—CF₃ (ortho) CH₂ Pyrazinyl NH—SO₂ Pyrrolyl None CH₂Pyrazinyl NH—SO₂ Pyrrolyl Z₁: F (2) CH₂ Pyrazinyl NH—SO₂ Pyrrolyl Z₁: F(3) CH₂ Pyrazinyl NH—SO₂ Pyrrolyl Z₁: F (2) Z₂: F (3) CH₂ PyrazinylNH—SO₂ Pyrrolyl Z₁: Cl (2) CH₂ Pyrazinyl NH—SO₂ Pyrrolyl Z₁: Cl (3) CH₂Pyrazinyl NH—SO₂ Pyrrolyl Z₁: Cl (2) Z₂: Cl (3) CH₂ Pyrazinyl NH—SO₂Pyrrolyl Z₁: F (2) Z₂: Cl (3) CH₂ Pyrazinyl NH—SO₂ Pyrrolyl Z₁: Cl (2)Z₂: F (3) CH₂ Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CH₃ (2) CH₂ Pyrazinyl NH—SO₂Pyrrolyl Z₁: CH₃ (3) CH₂ Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CH₃ (2) CH₂Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CH₃ (3) CH₂ Pyrazinyl NH—SO₂ PyrrolylZ₁: CH₂—CH₂—CH₃ or iPr (2) CH₂ Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CH₂—CH₃or iPr (3) CH₂ Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CH₂F (2) CH₂ PyrazinylNH—SO₂ Pyrrolyl Z₁: CH₂F (3) CH₂ Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CHF₂ (2)CH₂ Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CHF₂ (3) CH₂ Pyrazinyl NH—SO₂ PyrrolylZ₁: CF₃ (2) CH₂ Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CF₃ (3) CH₂ PyrazinylNH—SO₂ Pyrrolyl Z₁: CH₂—CH₂F (2) CH₂ Pyrazinyl NH—SO₂ Pyrrolyl Z₁:CH₂—CH₂F (3) CH₂ Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CHF₂ (2) CH₂Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CHF₂ (3) CH₂ Pyrazinyl NH—SO₂ PyrrolylZ₁: CH₂—CF₃ (2) CH₂ Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CF₃ (3) CH₂Pyrazinyl NH—SO₂ Imidazolyl None CH₂ Pyrazinyl NH—SO₂ Imidazolyl Z₁: F(2) CH₂ Pyrazinyl NH—SO₂ Imidazolyl Z₁: F (3) CH₂ Pyrazinyl NH—SO₂Imidazolyl Z₁: F (2) Z₂: F (3) CH₂ Pyrazinyl NH—SO₂ Imidazolyl Z₁: Cl(2) CH₂ Pyrazinyl NH—SO₂ Imidazolyl Z₁: Cl (3) CH₂ Pyrazinyl NH—SO₂Imidazolyl Z₁: Cl (2) Z₂: Cl (3) CH₂ Pyrazinyl NH—SO₂ Imidazolyl Z₁: F(2) Z₂: Cl (3) CH₂ Pyrazinyl NH—SO₂ Imidazolyl Z₁: Cl (2) Z₂: F (3) CH₂Pyrazinyl NH—SO₂ Imidazolyl Z₁: CH₃ (2) CH₂ Pyrazinyl NH—SO₂ ImidazolylZ₁: CH₃ (3) CH₂ Pyrazinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₃ (2) CH₂Pyrazinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₃ (3) CH₂ Pyrazinyl NH—SO₂Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂ Pyrazinyl NH—SO₂ ImidazolylZ₁: CH₂—CH₂—CH₃ or iPr (3) CH₂ Pyrazinyl NH—SO₂ Imidazolyl Z₁: CH₂F (2)CH₂ Pyrazinyl NH—SO₂ Imidazolyl Z₁: CH₂F (3) CH₂ Pyrazinyl NH—SO₂Imidazolyl Z₁: CHF₂ (2) CH₂ Pyrazinyl NH—SO₂ Imidazolyl Z₁: CHF₂ (3) CH₂Pyrazinyl NH—SO₂ Imidazolyl Z₁: CF₃ (2) CH₂ Pyrazinyl NH—SO₂ ImidazolylZ₁: CF₃ (3) CH₂ Pyrazinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₂F (2) CH₂Pyrazinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₂F (3) CH₂ Pyrazinyl NH—SO₂Imidazolyl Z₁: CH₂—CHF₂ (2) CH₂ Pyrazinyl NH—SO₂ Imidazolyl Z₁: CH₂—CHF₂(3) CH₂ Pyrazinyl NH—SO₂ Imidazolyl Z₁: CH₂—CF₃ (2) CH₂ Pyrazinyl NH—SO₂Imidazolyl Z₁: CH₂—CF₃ (3) CH₂ Pyrazinyl NH—SO₂ Furanyl None CH₂Pyrazinyl NH—SO₂ Furanyl Z₁: F (2) CH₂ Pyrazinyl NH—SO₂ Furanyl Z₁: F(3) CH₂ Pyrazinyl NH—SO₂ Furanyl Z₁: F (2) Z₂: F (3) CH₂ PyrazinylNH—SO₂ Furanyl Z₁: Cl (2) CH₂ Pyrazinyl NH—SO₂ Furanyl Z₁: Cl (3) CH₂Pyrazinyl NH—SO₂ Furanyl Z₁: Cl (2) Z₂: Cl (3) CH₂ Pyrazinyl NH—SO₂Furanyl Z₁: F (2) Z₂: Cl (3) CH₂ Pyrazinyl NH—SO₂ Furanyl Z₁: Cl (2) Z₂:F (3) CH₂ Pyrazinyl NH—SO₂ Furanyl Z₁: CH₃ (2) CH₂ Pyrazinyl NH—SO₂Furanyl Z₁: CH₃ (3) CH₂ Pyrazinyl NH—SO₂ Furanyl Z₁: CH₂—CH₃ (2) CH₂Pyrazinyl NH—SO₂ Furanyl Z₁: CH₂—CH₃ (3) CH₂ Pyrazinyl NH—SO₂ FuranylZ₁: CH₂—CH₂—CH₃ or iPr (2) CH₂ Pyrazinyl NH—SO₂ Furanyl Z₁: CH₂—CH₂—CH₃or iPr (3) CH₂ Pyrazinyl NH—SO₂ Furanyl Z₁: CH₂F (2) CH₂ PyrazinylNH—SO₂ Furanyl Z₁: CH₂F (3) CH₂ Pyrazinyl NH—SO₂ Furanyl Z₁: CHF₂ (2)CH₂ Pyrazinyl NH—SO₂ Furanyl Z₁: CHF₂ (3) CH₂ Pyrazinyl NH—SO₂ FuranylZ₁: CF₃ (2) CH₂ Pyrazinyl NH—SO₂ Furanyl Z₁: CF₃ (3) CH₂ PyrazinylNH—SO₂ Furanyl Z₁: CH₂—CH₂F (2) CH₂ Pyrazinyl NH—SO₂ Furanyl Z₁:CH₂—CH₂F (3) CH₂ Pyrazinyl NH—SO₂ Furanyl Z₁: CH₂—CHF₂ (2) CH₂ PyrazinylNH—SO₂ Furanyl Z₁: CH₂—CHF₂ (3) CH₂ Pyrazinyl NH—SO₂ Furanyl Z₁: CH₂—CF₃(2) CH₂ Pyrazinyl NH—SO₂ Furanyl Z₁: CH₂—CF₃ (3) CH₂ Pyrazinyl NH—SO₂Oxazolyl None CH₂ Pyrazinyl NH—SO₂ Oxazolyl Z₁: F (2) CH₂ PyrazinylNH—SO₂ Oxazolyl Z₁: F (3) CH₂ Pyrazinyl NH—SO₂ Oxazolyl Z₁: F (2) Z₂: F(3) CH₂ Pyrazinyl NH—SO₂ Oxazolyl Z₁: Cl (2) CH₂ Pyrazinyl NH—SO₂Oxazolyl Z₁: Cl (3) CH₂ Pyrazinyl NH—SO₂ Oxazolyl Z₁: Cl (2) Z₂: Cl (3)CH₂ Pyrazinyl NH—SO₂ Oxazolyl Z₁: F (2) Z₂: Cl (3) CH₂ Pyrazinyl NH—SO₂Oxazolyl Z₁: Cl (2) Z₂: F (3) CH₂ Pyrazinyl NH—SO₂ Oxazolyl Z₁: CH₃ (2)CH₂ Pyrazinyl NH—SO₂ Oxazolyl Z₁: CH₃ (3) CH₂ Pyrazinyl NH—SO₂ OxazolylZ₁: CH₂—CH₃ (2) CH₂ Pyrazinyl NH—SO₂ Oxazolyl Z₁: CH₂—CH₃ (3) CH₂Pyrazinyl NH—SO₂ Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂ PyrazinylNH—SO₂ Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CH₂ Pyrazinyl NH—SO₂ OxazolylZ₁: CH₂F (2) CH₂ Pyrazinyl NH—SO₂ Oxazolyl Z₁: CH₂F (3) CH₂ PyrazinylNH—SO₂ Oxazolyl Z₁: CHF₂ (2) CH₂ Pyrazinyl NH—SO₂ Oxazolyl Z₁: CHF₂ (3)CH₂ Pyrazinyl NH—SO₂ Oxazolyl Z₁: CF₃ (2) CH₂ Pyrazinyl NH—SO₂ OxazolylZ₁: CF₃ (3) CH₂ Pyrazinyl NH—SO₂ Oxazolyl Z₁: CH₂—CH₂F (2) CH₂ PyrazinylNH—SO₂ Oxazolyl Z₁: CH₂—CH₂F (3) CH₂ Pyrazinyl NH—SO₂ Oxazolyl Z₁:CH₂—CHF₂ (2) CH₂ Pyrazinyl NH—SO₂ Oxazolyl Z₁: CH₂—CHF₂ (3) CH₂Pyrazinyl NH—SO₂ Oxazolyl Z₁: CH₂—CF₃ (2) CH₂ Pyrazinyl NH—SO₂ OxazolylZ₁: CH₂—CF₃ (3) CH₂ Pyrazinyl NH—SO₂ Thiophenyl None CH₂ PyrazinylNH—SO₂ Thiophenyl Z₁: F (2) CH₂ Pyrazinyl NH—SO₂ Thiophenyl Z₁: F (3)CH₂ Pyrazinyl NH—SO₂ Thiophenyl Z₁: F (2) Z₂: F (3) CH₂ Pyrazinyl NH—SO₂Thiophenyl Z₁: Cl (2) CH₂ Pyrazinyl NH—SO₂ Thiophenyl Z₁: Cl (3) CH₂Pyrazinyl NH—SO₂ Thiophenyl Z₁: Cl (2) Z₂: Cl (3) CH₂ Pyrazinyl NH—SO₂Thiophenyl Z₁: F (2) Z₂: Cl (3) CH₂ Pyrazinyl NH—SO₂ Thiophenyl Z₁: Cl(2) Z₂: F (3) CH₂ Pyrazinyl NH—SO₂ Thiophenyl Z₁: CH₃ (2) CH₂ PyrazinylNH—SO₂ Thiophenyl Z₁: CH₃ (3) CH₂ Pyrazinyl NH—SO₂ Thiophenyl Z₁:CH₂—CH₃ (2) CH₂ Pyrazinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₃ (3) CH₂Pyrazinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂ PyrazinylNH—SO₂ Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CH₂ Pyrazinyl NH—SO₂Thiophenyl Z₁: CH₂F (2) CH₂ Pyrazinyl NH—SO₂ Thiophenyl Z₁: CH₂F (3) CH₂Pyrazinyl NH—SO₂ Thiophenyl Z₁: CHF₂ (2) CH₂ Pyrazinyl NH—SO₂ ThiophenylZ₁: CHF₂ (3) CH₂ Pyrazinyl NH—SO₂ Thiophenyl Z₁: CF₃ (2) CH₂ PyrazinylNH—SO₂ Thiophenyl Z₁: CF₃ (3) CH₂ Pyrazinyl NH—SO₂ Thiophenyl Z₁:CH₂—CH₂F (2) CH₂ Pyrazinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₂F (3) CH₂Pyrazinyl NH—SO₂ Thiophenyl Z₁: CH₂—CHF₂ (2) CH₂ Pyrazinyl NH—SO₂Thiophenyl Z₁: CH₂—CHF₂ (3) CH₂ Pyrazinyl NH—SO₂ Thiophenyl Z₁: CH₂—CF₃(2) CH₂ Pyrazinyl NH—SO₂ Thiophenyl Z₁: CH₂—CF₃ (3) CH₂ Pyrazinyl NH—SO₂Thiazolyl None CH₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁: F (2) CH₂ PyrazinylNH—SO₂ Thiazolyl Z₁: F (3) CH₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁: F (2) Z₂:F (3) CH₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁: Cl (2) CH₂ Pyrazinyl NH—SO₂Thiazolyl Z₁: Cl (3) CH₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁: Cl (2) Z₂: Cl(3) CH₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁: F (2) Z₂: Cl (3) CH₂ PyrazinylNH—SO₂ Thiazolyl Z₁: Cl (2) Z₂: F (3) CH₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁:CH₃ (2) CH₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁: CH₃ (3) CH₂ Pyrazinyl NH—SO₂Thiazolyl Z₁: CH₂—CH₃ (2) CH₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₃ (3)CH₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CH₂ PyrazinylNH—SO₂ Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CH₂ Pyrazinyl NH—SO₂Thiazolyl Z₁: CH₂F (2) CH₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁: CH₂F (3) CH₂Pyrazinyl NH—SO₂ Thiazolyl Z₁: CHF₂ (2) CH₂ Pyrazinyl NH—SO₂ ThiazolylZ₁: CHF₂ (3) CH₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁: CF₃ (2) CH₂ PyrazinylNH—SO₂ Thiazolyl Z₁: CF₃ (3) CH₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₂F(2) CH₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₂F (3) CH₂ Pyrazinyl NH—SO₂Thiazolyl Z₁: CH₂—CHF₂ (2) CH₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁: CH₂—CHF₂(3) CH₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁: CH₂—CF₃ (2) CH₂ Pyrazinyl NH—SO₂Thiazolyl Z₁: CH₂—CF₃ (3) CF₂ pyridinyl NH—CH₂ Phenyl None CF₂ pyridinylNH—CH₂ Phenyl Z₁: F (para) CF₂ pyridinyl NH—CH₂ phenyl Z₁: F (meta) CF₂pyridinyl NH—CH₂ phenyl Z₁: F (ortho) CF₂ pyridinyl NH—CH₂ phenyl Z₁: F(para) Z₂: F (meta) CF₂ Pyridinyl NH—CH₂ Phenyl Z₁: Cl (meta) CF₂Pyridinyl NH—CH₂ Phenyl Z₁: Cl (para) CF₂ Pyridinyl NH—CH₂ Phenyl Z₁: Cl(para) Z₂: Cl (meta) CF₂ Pyridinyl NH—CH₂ Phenyl Z₁: F (para) Z₂: Cl(meta) CF₂ Pyridinyl NH—CH₂ Phenyl Z₁: Cl (para) Z₂: F (meta) CF₂Pyridinyl NH—CH₂ Phenyl Z₁: CH₃ (para) CF₂ Pyridinyl NH—CH₂ Phenyl Z₁:CH₃ (meta) CF₂ Pyridinyl NH—CH₂ Phenyl Z₁: CH₃ (ortho) CF₂ PyridinylNH—CH₂ Phenyl Z₁: CH₂—CH₃ (para) CF₂ Pyridinyl NH—CH₂ Phenyl Z₁: CH₂—CH₃(meta) CF₂ Pyridinyl NH—CH₂ Phenyl Z₁: CH₂—CH₃ (ortho) CF₂ PyridinylNH—CH₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CF₂ Pyridinyl NH—CH₂ PhenylZ₁: CH₂—CH₂—CH₃ or iPr (meta) CF₂ Pyridinyl NH—CH₂ Phenyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyridinyl NH—CH₂ Phenyl Z₁: CH₂F (para)CF₂ Pyridinyl NH—CH₂ Phenyl Z₁: CH₂F (meta) CF₂ Pyridinyl NH—CH₂ PhenylZ₁: CH₂F (ortho) CF₂ Pyridinyl NH—CH₂ Phenyl Z₁: CHF₂ (para) CF₂Pyridinyl NH—CH₂ Phenyl Z₁: CHF₂ (meta) CF₂ Pyridinyl NH—CH₂ Phenyl Z₁:CHF₂ (ortho) CF₂ Pyridinyl NH—CH₂ Phenyl Z₁: CF₃ (para) CF₂ PyridinylNH—CH₂ Phenyl Z₁: CF₃ (meta) CF₂ Pyridinyl NH—CH₂ Phenyl Z₁: CF₃ (ortho)CF₂ Pyridinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂F (para) CF₂ Pyridinyl NH—CH₂Phenyl Z₁: CH₂—CH₂F (meta) CF₂ Pyridinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂F(ortho) CF₂ Pyridinyl NH—CH₂ Phenyl Z₁: CH₂—CHF₂ (para) CF₂ PyridinylNH—CH₂ Phenyl Z₁: CH₂—CHF₂ (meta) CF₂ Pyridinyl NH—CH₂ Phenyl Z₁:CH₂—CHF₂ (ortho) CF₂ Pyridinyl NH—CH₂ Phenyl Z₁: CH₂—CF₃ (para) CF₂Pyridinyl NH—CH₂ Phenyl Z₁: CH₂—CF₃ (meta) CF₂ Pyridinyl NH—CH₂ PhenylZ₁: CH₂—CF₃ (ortho) CF₂ pyridinyl NH—CH₂ Pyridinyl None CF₂ pyridinylNH—CH₂ Pyridinyl Z₁: F (para) CF₂ pyridinyl NH—CH₂ Pyridinyl Z₁: F(meta) CF₂ pyridinyl NH—CH₂ Pyridinyl Z₁: F (ortho) CF₂ pyridinyl NH—CH₂Pyridinyl Z₁: F (para) Z₂: F (meta) CF₂ Pyridinyl NH—CH₂ Pyridinyl Z₁:Cl (meta) CF₂ Pyridinyl NH—CH₂ Pyridinyl Z₁: Cl (para) CF₂ PyridinylNH—CH₂ Pyridinyl Z₁: Cl (para) Z₂: Cl (meta) CF₂ Pyridinyl NH—CH₂Pyridinyl Z₁: F (para) Z₂: Cl (meta) CF₂ Pyridinyl NH—CH₂ Pyridinyl Z₁:Cl (para) Z₂: F (meta) CF₂ Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₃ (para) CF₂Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₃ (meta) CF₂ Pyridinyl NH—CH₂ PyridinylZ₁: CH₃ (ortho) CF₂ Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₃ (para) CF₂Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₃ (meta) CF₂ Pyridinyl NH—CH₂Pyridinyl Z₁: CH₂—CH₃ (ortho) CF₂ Pyridinyl NH—CH₂ Pyridinyl Z₁:CH₂—CH₂—CH₃ or iPr (para) CF₂ Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₂—CH₃or iPr (meta) CF₂ Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr(ortho) CF₂ Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₂F (para) CF₂ PyridinylNH—CH₂ Pyridinyl Z₁: CH₂F (meta) CF₂ Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₂F(ortho) CF₂ Pyridinyl NH—CH₂ Pyridinyl Z₁: CHF₂ (para) CF₂ PyridinylNH—CH₂ Pyridinyl Z₁: CHF₂ (meta) CF₂ Pyridinyl NH—CH₂ Pyridinyl Z₁: CHF₂(ortho) CF₂ Pyridinyl NH—CH₂ Pyridinyl Z₁: CF₃ (para) CF₂ PyridinylNH—CH₂ Pyridinyl Z₁: CF₃ (meta) CF₂ Pyridinyl NH—CH₂ Pyridinyl Z₁: CF₃(ortho) CF₂ Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₂F (para) CF₂ PyridinylNH—CH₂ Pyridinyl Z₁: CH₂—CH₂F (meta) CF₂ Pyridinyl NH—CH₂ Pyridinyl Z₁:CH₂—CH₂F (ortho) CF₂ Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₂—CHF₂ (para) CF₂Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₂—CHF₂ (meta) CF₂ Pyridinyl NH—CH₂Pyridinyl Z₁: CH₂—CHF₂ (ortho) CF₂ Pyridinyl NH—CH₂ Pyridinyl Z₁:CH₂—CF₃ (para) CF₂ Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₂—CF₃ (meta) CF₂Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₂—CF₃ (ortho) CF₂ pyridinyl NH—CH₂Pyrimidinyl None CF₂ pyridinyl NH—CH₂ Pyrimidinyl Z₁: F (para) CF₂pyridinyl NH—CH₂ Pyrimidinyl Z₁: F (meta) CF₂ pyridinyl NH—CH₂Pyrimidinyl Z₁: F (ortho) CF₂ pyridinyl NH—CH₂ Pyrimidinyl Z₁: F (para)Z₂: F (meta) CF₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁: Cl (meta) CF₂Pyridinyl NH—CH₂ Pyrimidinyl Z₁: Cl (para) CF₂ Pyridinyl NH—CH₂Pyrimidinyl Z₁: Cl (para) Z₂: Cl (meta) CF₂ Pyridinyl NH—CH₂ PyrimidinylZ₁: F (para) Z₂: Cl (meta) CF₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁: Cl(para) Z₂: F (meta) CF₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₃ (para) CF₂Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₃ (meta) CF₂ Pyridinyl NH—CH₂Pyrimidinyl Z₁: CH₃ (ortho) CF₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₃(para) CF₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₃ (meta) CF₂ PyridinylNH—CH₂ Pyrimidinyl Z₁: CH₂—CH₃ (ortho) CF₂ Pyridinyl NH—CH₂ PyrimidinylZ₁: CH₂—CH₂—CH₃ or iPr (para) CF₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) CF₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₂F(para) CF₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₂F (meta) CF₂ PyridinylNH—CH₂ Pyrimidinyl Z₁: CH₂F (ortho) CF₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁:CHF₂ (para) CF₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CHF₂ (meta) CF₂Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CHF₂ (ortho) CF₂ Pyridinyl NH—CH₂Pyrimidinyl Z₁: CF₃ (para) CF₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CF₃(meta) CF₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CF₃ (ortho) CF₂ PyridinylNH—CH₂ Pyrimidinyl Z₁: CH₂—CH₂F (para) CF₂ Pyridinyl NH—CH₂ PyrimidinylZ₁: CH₂—CH₂F (meta) CF₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₂F(ortho) CF₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CHF₂ (para) CF₂Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CHF₂ (meta) CF₂ Pyridinyl NH—CH₂Pyrimidinyl Z₁: CH₂—CHF₂ (ortho) CF₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁:CH₂—CF₃ (para) CF₂ Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CF₃ (meta) CF₂Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CF₃ (ortho) CF₂ pyridinyl NH—CH₂Pyrazinyl None CF₂ pyridinyl NH—CH₂ Pyrazinyl Z₁: F (para) CF₂ pyridinylNH—CH₂ Pyrazinyl Z₁: F (meta) CF₂ pyridinyl NH—CH₂ Pyrazinyl Z₁: F(ortho) CF₂ pyridinyl NH—CH₂ Pyrazinyl Z₁: F (para) Z₂: F (meta) CF₂Pyridinyl NH—CH₂ Pyrazinyl Z₁: Cl (meta) CF₂ Pyridinyl NH—CH₂ PyrazinylZ₁: Cl (para) CF₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁: Cl (para) Z₂: Cl (meta)CF₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁: F (para) Z₂: Cl (meta) CF₂ PyridinylNH—CH₂ Pyrazinyl Z₁: Cl (para) Z₂: F (meta) CF₂ Pyridinyl NH—CH₂Pyrazinyl Z₁: CH₃ (para) CF₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₃ (meta)CF₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₃ (ortho) CF₂ Pyridinyl NH—CH₂Pyrazinyl Z₁: CH₂—CH₃ (para) CF₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₃(meta) CF₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₃ (ortho) CF₂ PyridinylNH—CH₂ Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CF₂ Pyridinyl NH—CH₂Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CF₂ Pyridinyl NH—CH₂ PyrazinylZ₁: CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂F(para) CF₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂F (meta) CF₂ PyridinylNH—CH₂ Pyrazinyl Z₁: CH₂F (ortho) CF₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁:CHF₂ (para) CF₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁: CHF₂ (meta) CF₂ PyridinylNH—CH₂ Pyrazinyl Z₁: CHF₂ (ortho) CF₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁: CF₃(para) CF₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁: CF₃ (meta) CF₂ PyridinylNH—CH₂ Pyrazinyl Z₁: CF₃ (ortho) CF₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁:CH₂—CH₂F (para) CF₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₂F (meta) CF₂Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₂F (ortho) CF₂ Pyridinyl NH—CH₂Pyrazinyl Z₁: CH₂—CHF₂ (para) CF₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁:CH₂—CHF₂ (meta) CF₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CHF₂ (ortho) CF₂Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CF₃ (para) CF₂ Pyridinyl NH—CH₂Pyrazinyl Z₁: CH₂—CF₃ (meta) CF₂ Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CF₃(ortho) CF₂ pyridinyl NH—CH₂ Pyrrolyl None CF₂ pyridinyl NH—CH₂ PyrrolylZ₁: F (2) CF₂ pyridinyl NH—CH₂ Pyrrolyl Z₁: F (3) CF₂ pyridinyl NH—CH₂Pyrrolyl Z₁: F (2) Z₂: F (3) CF₂ Pyridinyl NH—CH₂ Pyrrolyl Z₁: Cl (2)CF₂ Pyridinyl NH—CH₂ Pyrrolyl Z₁: Cl (3) CF₂ Pyridinyl NH—CH₂ PyrrolylZ₁: Cl (2) Z₂: Cl (3) CF₂ Pyridinyl NH—CH₂ Pyrrolyl Z₁: F (2) Z₂: Cl (3)CF₂ Pyridinyl NH—CH₂ Pyrrolyl Z₁: Cl (2) Z₂: F (3) CF₂ Pyridinyl NH—CH₂Pyrrolyl Z₁: CH₃ (2) CF₂ Pyridinyl NH—CH₂ Pyrrolyl Z₁: CH₃ (3) CF₂Pyridinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₃ (2) CF₂ Pyridinyl NH—CH₂ PyrrolylZ₁: CH₂—CH₃ (3) CF₂ Pyridinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (2)CF₂ Pyridinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CF₂ PyridinylNH—CH₂ Pyrrolyl Z₁: CH₂F (2) CF₂ Pyridinyl NH—CH₂ Pyrrolyl Z₁: CH₂F (3)CF₂ Pyridinyl NH—CH₂ Pyrrolyl Z₁: CHF₂ (2) CF₂ Pyridinyl NH—CH₂ PyrrolylZ₁: CHF₂ (3) CF₂ Pyridinyl NH—CH₂ Pyrrolyl Z₁: CF₃ (2) CF₂ PyridinylNH—CH₂ Pyrrolyl Z₁: CF₃ (3) CF₂ Pyridinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₂F(2) CF₂ Pyridinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₂F (3) CF₂ Pyridinyl NH—CH₂Pyrrolyl Z₁: CH₂—CHF₂ (2) CF₂ Pyridinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CHF₂ (3)CF₂ Pyridinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CF₃ (2) CF₂ Pyridinyl NH—CH₂Pyrrolyl Z₁: CH₂—CF₃ (3) CF₂ pyridinyl NH—CH₂ Imidazolyl None CF₂pyridinyl NH—CH₂ Imidazolyl Z₁: F (2) CF₂ pyridinyl NH—CH₂ ImidazolylZ₁: F (3) CF₂ pyridinyl NH—CH₂ Imidazolyl Z₁: F (2) Z₂: F (3) CF₂Pyridinyl NH—CH₂ Imidazolyl Z₁: Cl (2) CF₂ Pyridinyl NH—CH₂ ImidazolylZ₁: Cl (3) CF₂ Pyridinyl NH—CH₂ Imidazolyl Z₁: Cl (2) Z₂: Cl (3) CF₂Pyridinyl NH—CH₂ Imidazolyl Z₁: F (2) Z₂: Cl (3) CF₂ Pyridinyl NH—CH₂Imidazolyl Z₁: Cl (2) Z₂: F (3) CF₂ Pyridinyl NH—CH₂ Imidazolyl Z₁: CH₃(2) CF₂ Pyridinyl NH—CH₂ Imidazolyl Z₁: CH₃ (3) CF₂ Pyridinyl NH—CH₂Imidazolyl Z₁: CH₂—CH₃ (2) CF₂ Pyridinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₃(3) CF₂ Pyridinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂Pyridinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CF₂ PyridinylNH—CH₂ Imidazolyl Z₁: CH₂F (2) CF₂ Pyridinyl NH—CH₂ Imidazolyl Z₁: CH₂F(3) CF₂ Pyridinyl NH—CH₂ Imidazolyl Z₁: CHF₂ (2) CF₂ Pyridinyl NH—CH₂Imidazolyl Z₁: CHF₂ (3) CF₂ Pyridinyl NH—CH₂ Imidazolyl Z₁: CF₃ (2) CF₂Pyridinyl NH—CH₂ Imidazolyl Z₁: CF₃ (3) CF₂ Pyridinyl NH—CH₂ ImidazolylZ₁: CH₂—CH₂F (2) CF₂ Pyridinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₂F (3) CF₂Pyridinyl NH—CH₂ Imidazolyl Z₁: CH₂—CHF₂ (2) CF₂ Pyridinyl NH—CH₂Imidazolyl Z₁: CH₂—CHF₂ (3) CF₂ Pyridinyl NH—CH₂ Imidazolyl Z₁: CH₂—CF₃(2) CF₂ Pyridinyl NH—CH₂ Imidazolyl Z₁: CH₂—CF₃ (3) CF₂ pyridinyl NH—CH₂Furanyl None CF₂ pyridinyl NH—CH₂ Furanyl Z₁: F (2) CF₂ pyridinyl NH—CH₂Furanyl Z₁: F (3) CF₂ pyridinyl NH—CH₂ Furanyl Z₁: F (2) Z₂: F (3) CF₂Pyridinyl NH—CH₂ Furanyl Z₁: Cl (2) CF₂ Pyridinyl NH—CH₂ Furanyl Z₁: Cl(3) CF₂ Pyridinyl NH—CH₂ Furanyl Z₁: Cl (2) Z₂: Cl (3) CF₂ PyridinylNH—CH₂ Furanyl Z₁: F (2) Z₂: Cl (3) CF₂ Pyridinyl NH—CH₂ Furanyl Z₁: Cl(2) Z₂: F (3) CF₂ Pyridinyl NH—CH₂ Furanyl Z₁: CH₃ (2) CF₂ PyridinylNH—CH₂ Furanyl Z₁: CH₃ (3) CF₂ Pyridinyl NH—CH₂ Furanyl Z₁: CH₂—CH₃ (2)CF₂ Pyridinyl NH—CH₂ Furanyl Z₁: CH₂—CH₃ (3) CF₂ Pyridinyl NH—CH₂Furanyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂ Pyridinyl NH—CH₂ Furanyl Z₁:CH₂—CH₂—CH₃ or iPr (3) CF₂ Pyridinyl NH—CH₂ Furanyl Z₁: CH₂F (2) CF₂Pyridinyl NH—CH₂ Furanyl Z₁: CH₂F (3) CF₂ Pyridinyl NH—CH₂ Furanyl Z₁:CHF₂ (2) CF₂ Pyridinyl NH—CH₂ Furanyl Z₁: CHF₂ (3) CF₂ Pyridinyl NH—CH₂Furanyl Z₁: CF₃ (2) CF₂ Pyridinyl NH—CH₂ Furanyl Z₁: CF₃ (3) CF₂Pyridinyl NH—CH₂ Furanyl Z₁: CH₂—CH₂F (2) CF₂ Pyridinyl NH—CH₂ FuranylZ₁: CH₂—CH₂F (3) CF₂ Pyridinyl NH—CH₂ Furanyl Z₁: CH₂—CHF₂ (2) CF₂Pyridinyl NH—CH₂ Furanyl Z₁: CH₂—CHF₂ (3) CF₂ Pyridinyl NH—CH₂ FuranylZ₁: CH₂—CF₃ (2) CF₂ Pyridinyl NH—CH₂ Furanyl Z₁: CH₂—CF₃ (3) CF₂pyridinyl NH—CH₂ Oxazolyl None CF₂ pyridinyl NH—CH₂ Oxazolyl Z₁: F (2)CF₂ pyridinyl NH—CH₂ Oxazolyl Z₁: F (3) CF₂ pyridinyl NH—CH₂ OxazolylZ₁: F (2) Z₂: F (3) CF₂ Pyridinyl NH—CH₂ Oxazolyl Z₁: Cl (2) CF₂Pyridinyl NH—CH₂ Oxazolyl Z₁: Cl (3) CF₂ Pyridinyl NH—CH₂ Oxazolyl Z₁:Cl (2) Z₂: Cl (3) CF₂ Pyridinyl NH—CH₂ Oxazolyl Z₁: F (2) Z₂: Cl (3) CF₂Pyridinyl NH—CH₂ Oxazolyl Z₁: Cl (2) Z₂: F (3) CF₂ Pyridinyl NH—CH₂Oxazolyl Z₁: CH₃ (2) CF₂ Pyridinyl NH—CH₂ Oxazolyl Z₁: CH₃ (3) CF₂Pyridinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₃ (2) CF₂ Pyridinyl NH—CH₂ OxazolylZ₁: CH₂—CH₃ (3) CF₂ Pyridinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2)CF₂ Pyridinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CF₂ PyridinylNH—CH₂ Oxazolyl Z₁: CH₂F (2) CF₂ Pyridinyl NH—CH₂ Oxazolyl Z₁: CH₂F (3)CF₂ Pyridinyl NH—CH₂ Oxazolyl Z₁: CHF₂ (2) CF₂ Pyridinyl NH—CH₂ OxazolylZ₁: CHF₂ (3) CF₂ Pyridinyl NH—CH₂ Oxazolyl Z₁: CF₃ (2) CF₂ PyridinylNH—CH₂ Oxazolyl Z₁: CF₃ (3) CF₂ Pyridinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₂F(2) CF₂ Pyridinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₂F (3) CF₂ Pyridinyl NH—CH₂Oxazolyl Z₁: CH₂—CHF₂ (2) CF₂ Pyridinyl NH—CH₂ Oxazolyl Z₁: CH₂—CHF₂ (3)CF₂ Pyridinyl NH—CH₂ Oxazolyl Z₁: CH₂—CF₃ (2) CF₂ Pyridinyl NH—CH₂Oxazolyl Z₁: CH₂—CF₃ (3) CF₂ pyridinyl NH—CH₂ Thiophenyl None CF₂pyridinyl NH—CH₂ Thiophenyl Z₁: F (2) CF₂ pyridinyl NH—CH₂ ThiophenylZ₁: F (3) CF₂ pyridinyl NH—CH₂ Thiophenyl Z₁: F (2) Z₂: F (3) CF₂Pyridinyl NH—CH₂ Thiophenyl Z₁: Cl (2) CF₂ Pyridinyl NH—CH₂ ThiophenylZ₁: Cl (3) CF₂ Pyridinyl NH—CH₂ Thiophenyl Z₁: Cl (2) Z₂: Cl (3) CF₂Pyridinyl NH—CH₂ Thiophenyl Z₁: F (2) Z₂: Cl (3) CF₂ Pyridinyl NH—CH₂Thiophenyl Z₁: Cl (2) Z₂: F (3) CF₂ Pyridinyl NH—CH₂ Thiophenyl Z₁: CH₃(2) CF₂ Pyridinyl NH—CH₂ Thiophenyl Z₁: CH₃ (3) CF₂ Pyridinyl NH—CH₂Thiophenyl Z₁: CH₂—CH₃ (2) CF₂ Pyridinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₃(3) CF₂ Pyridinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂Pyridinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CF₂ PyridinylNH—CH₂ Thiophenyl Z₁: CH₂F (2) CF₂ Pyridinyl NH—CH₂ Thiophenyl Z₁: CH₂F(3) CF₂ Pyridinyl NH—CH₂ Thiophenyl Z₁: CHF₂ (2) CF₂ Pyridinyl NH—CH₂Thiophenyl Z₁: CHF₂ (3) CF₂ Pyridinyl NH—CH₂ Thiophenyl Z₁: CF₃ (2) CF₂Pyridinyl NH—CH₂ Thiophenyl Z₁: CF₃ (3) CF₂ Pyridinyl NH—CH₂ ThiophenylZ₁: CH₂—CH₂F (2) CF₂ Pyridinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₂F (3) CF₂Pyridinyl NH—CH₂ Thiophenyl Z₁: CH₂—CHF₂ (2) CF₂ Pyridinyl NH—CH₂Thiophenyl Z₁: CH₂—CHF₂ (3) CF₂ Pyridinyl NH—CH₂ Thiophenyl Z₁: CH₂—CF₃(2) CF₂ Pyridinyl NH—CH₂ Thiophenyl Z₁: CH₂—CF₃ (3) CF₂ pyridinyl NH—CH₂Thiazolyl None CF₂ pyridinyl NH—CH₂ Thiazolyl Z₁: F (2) CF₂ pyridinylNH—CH₂ Thiazolyl Z₁: F (3) CF₂ pyridinyl NH—CH₂ Thiazolyl Z₁: F (2) Z₂:F (3) CF₂ Pyridinyl NH—CH₂ Thiazolyl Z₁: Cl (2) CF₂ Pyridinyl NH—CH₂Thiazolyl Z₁: Cl (3) CF₂ Pyridinyl NH—CH₂ Thiazolyl Z₁: Cl (2) Z₂: Cl(3) CF₂ Pyridinyl NH—CH₂ Thiazolyl Z₁: F (2) Z₂: Cl (3) CF₂ PyridinylNH—CH₂ Thiazolyl Z₁: Cl (2) Z₂: F (3) CF₂ Pyridinyl NH—CH₂ Thiazolyl Z₁:CH₃ (2) CF₂ Pyridinyl NH—CH₂ Thiazolyl Z₁: CH₃ (3) CF₂ Pyridinyl NH—CH₂Thiazolyl Z₁: CH₂—CH₃ (2) CF₂ Pyridinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₃ (3)CF₂ Pyridinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂ PyridinylNH—CH₂ Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CF₂ Pyridinyl NH—CH₂Thiazolyl Z₁: CH₂F (2) CF₂ Pyridinyl NH—CH₂ Thiazolyl Z₁: CH₂F (3) CF₂Pyridinyl NH—CH₂ Thiazolyl Z₁: CHF₂ (2) CF₂ Pyridinyl NH—CH₂ ThiazolylZ₁: CHF₂ (3) CF₂ Pyridinyl NH—CH₂ Thiazolyl Z₁: CF₃ (2) CF₂ PyridinylNH—CH₂ Thiazolyl Z₁: CF₃ (3) CF₂ Pyridinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₂F(2) CF₂ Pyridinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₂F (3) CF₂ Pyridinyl NH—CH₂Thiazolyl Z₁: CH₂—CHF₂ (2) CF₂ Pyridinyl NH—CH₂ Thiazolyl Z₁: CH₂—CHF₂(3) CF₂ Pyridinyl NH—CH₂ Thiazolyl Z₁: CH₂—CF₃ (2) CF₂ Pyridinyl NH—CH₂Thiazolyl Z₁: CH₂—CF₃ (3) CF₂ pyridinyl NH—C(O) Phenyl None CF₂pyridinyl NH—C(O) Phenyl Z₁: F (para) CF₂ pyridinyl NH—C(O) phenyl Z₁: F(meta) CF₂ pyridinyl NH—C(O) phenyl Z₁: F (ortho) CF₂ pyridinyl NH—C(O)phenyl Z₁: F (para) Z₂: F (meta) CF₂ Pyridinyl NH—C(O) Phenyl Z₁: Cl(meta) CF₂ Pyridinyl NH—C(O) Phenyl Z₁: Cl (para) CF₂ Pyridinyl NH—C(O)Phenyl Z₁: Cl (para) Z₂: Cl (meta) CF₂ Pyridinyl NH—C(O) Phenyl Z₁: F(para) Z₂: Cl (meta) CF₂ Pyridinyl NH—C(O) Phenyl Z₁: Cl (para) Z₂: F(meta) CF₂ Pyridinyl NH—C(O) Phenyl Z₁: CH₃ (para) CF₂ Pyridinyl NH—C(O)Phenyl Z₁: CH₃ (meta) CF₂ Pyridinyl NH—C(O) Phenyl Z₁: CH₃ (ortho) CF₂Pyridinyl NH—C(O) Phenyl Z₁: CH₂—CH₃ (para) CF₂ Pyridinyl NH—C(O) PhenylZ₁: CH₂—CH₃ (meta) CF₂ Pyridinyl NH—C(O) Phenyl Z₁: CH₂—CH₃ (ortho) CF₂Pyridinyl NH—C(O) Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CF₂ PyridinylNH—C(O) Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CF₂ Pyridinyl NH—C(O)Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyridinyl NH—C(O) Phenyl Z₁:CH₂F (para) CF₂ Pyridinyl NH—C(O) Phenyl Z₁: CH₂F (meta) CF₂ PyridinylNH—C(O) Phenyl Z₁: CH₂F (ortho) CF₂ Pyridinyl NH—C(O) Phenyl Z₁: CHF₂(para) CF₂ Pyridinyl NH—C(O) Phenyl Z₁: CHF₂ (meta) CF₂ PyridinylNH—C(O) Phenyl Z₁: CHF₂ (ortho) CF₂ Pyridinyl NH—C(O) Phenyl Z₁: CF₃(para) CF₂ Pyridinyl NH—C(O) Phenyl Z₁: CF₃ (meta) CF₂ Pyridinyl NH—C(O)Phenyl Z₁: CF₃ (ortho) CF₂ Pyridinyl NH—C(O) Phenyl Z₁: CH₂—CH₂F (para)CF₂ Pyridinyl NH—C(O) Phenyl Z₁: CH₂—CH₂F (meta) CF₂ Pyridinyl NH—C(O)Phenyl Z₁: CH₂—CH₂F (ortho) CF₂ Pyridinyl NH—C(O) Phenyl Z₁: CH₂—CHF₂(para) CF₂ Pyridinyl NH—C(O) Phenyl Z₁: CH₂—CHF₂ (meta) CF₂ PyridinylNH—C(O) Phenyl Z₁: CH₂—CHF₂ (ortho) CF₂ Pyridinyl NH—C(O) Phenyl Z₁:CH₂—CF₃ (para) CF₂ Pyridinyl NH—C(O) Phenyl Z₁: CH₂—CF₃ (meta) CF₂Pyridinyl NH—C(O) Phenyl Z₁: CH₂—CF₃ (ortho) CF₂ pyridinyl NH—C(O)Pyridinyl None CF₂ pyridinyl NH—C(O) Pyridinyl Z₁: F (para) CF₂pyridinyl NH—C(O) Pyridinyl Z₁: F (meta) CF₂ pyridinyl NH—C(O) PyridinylZ₁: F (ortho) CF₂ pyridinyl NH—C(O) Pyridinyl Z₁: F (para) Z₂: F (meta)CF₂ Pyridinyl NH—C(O) Pyridinyl Z₁: Cl (meta) CF₂ Pyridinyl NH—C(O)Pyridinyl Z₁: Cl (para) CF₂ Pyridinyl NH—C(O) Pyridinyl Z₁: Cl (para)Z₂: Cl (meta) CF₂ Pyridinyl NH—C(O) Pyridinyl Z₁: F (para) Z₂: Cl (meta)CF₂ Pyridinyl NH—C(O) Pyridinyl Z₁: Cl (para) Z₂: F (meta) CF₂ PyridinylNH—C(O) Pyridinyl Z₁: CH₃ (para) CF₂ Pyridinyl NH—C(O) Pyridinyl Z₁: CH₃(meta) CF₂ Pyridinyl NH—C(O) Pyridinyl Z₁: CH₃ (ortho) CF₂ PyridinylNH—C(O) Pyridinyl Z₁: CH₂—CH₃ (para) CF₂ Pyridinyl NH—C(O) Pyridinyl Z₁:CH₂—CH₃ (meta) CF₂ Pyridinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₃ (ortho) CF₂Pyridinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CF₂ PyridinylNH—C(O) Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CF₂ Pyridinyl NH—C(O)Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyridinyl NH—C(O) PyridinylZ₁: CH₂F (para) CF₂ Pyridinyl NH—C(O) Pyridinyl Z₁: CH₂F (meta) CF₂Pyridinyl NH—C(O) Pyridinyl Z₁: CH₂F (ortho) CF₂ Pyridinyl NH—C(O)Pyridinyl Z₁: CHF₂ (para) CF₂ Pyridinyl NH—C(O) Pyridinyl Z₁: CHF₂(meta) CF₂ Pyridinyl NH—C(O) Pyridinyl Z₁: CHF₂ (ortho) CF₂ PyridinylNH—C(O) Pyridinyl Z₁: CF₃ (para) CF₂ Pyridinyl NH—C(O) Pyridinyl Z₁: CF₃(meta) CF₂ Pyridinyl NH—C(O) Pyridinyl Z₁: CF₃ (ortho) CF₂ PyridinylNH—C(O) Pyridinyl Z₁: CH₂—CH₂F (para) CF₂ Pyridinyl NH—C(O) PyridinylZ₁: CH₂—CH₂F (meta) CF₂ Pyridinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₂F (ortho)CF₂ Pyridinyl NH—C(O) Pyridinyl Z₁: CH₂—CHF₂ (para) CF₂ PyridinylNH—C(O) Pyridinyl Z₁: CH₂—CHF₂ (meta) CF₂ Pyridinyl NH—C(O) PyridinylZ₁: CH₂—CHF₂ (ortho) CF₂ Pyridinyl NH—C(O) Pyridinyl Z₁: CH₂—CF₃ (para)CF₂ Pyridinyl NH—C(O) Pyridinyl Z₁: CH₂—CF₃ (meta) CF₂ Pyridinyl NH—C(O)Pyridinyl Z₁: CH₂—CF₃ (ortho) CF₂ pyridinyl NH—C(O) Pyrimidinyl None CF₂pyridinyl NH—C(O) Pyrimidinyl Z₁: F (para) CF₂ pyridinyl NH—C(O)Pyrimidinyl Z₁: F (meta) CF₂ pyridinyl NH—C(O) Pyrimidinyl Z₁: F (ortho)CF₂ pyridinyl NH—C(O) Pyrimidinyl Z₁: F (para) Z₂: F (meta) CF₂Pyridinyl NH—C(O) Pyrimidinyl Z₁: Cl (meta) CF₂ Pyridinyl NH—C(O)Pyrimidinyl Z₁: Cl (para) CF₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁: Cl(para) Z₂: Cl (meta) CF₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁: F (para) Z₂:Cl (meta) CF₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁: Cl (para) Z₂: F (meta)CF₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁: CH₃ (para) CF₂ Pyridinyl NH—C(O)Pyrimidinyl Z₁: CH₃ (meta) CF₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁: CH₃(ortho) CF₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CH₃ (para) CF₂Pyridinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CH₃ (meta) CF₂ Pyridinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CH₃ (ortho) CF₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (para) CF₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) CF₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁: CH₂F(para) CF₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁: CH₂F (meta) CF₂ PyridinylNH—C(O) Pyrimidinyl Z₁: CH₂F (ortho) CF₂ Pyridinyl NH—C(O) PyrimidinylZ₁: CHF₂ (para) CF₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁: CHF₂ (meta) CF₂Pyridinyl NH—C(O) Pyrimidinyl Z₁: CHF₂ (ortho) CF₂ Pyridinyl NH—C(O)Pyrimidinyl Z₁: CF₃ (para) CF₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁: CF₃(meta) CF₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁: CF₃ (ortho) CF₂ PyridinylNH—C(O) Pyrimidinyl Z₁: CH₂—CH₂F (para) CF₂ Pyridinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CH₂F (meta) CF₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CH₂F (ortho) CF₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CHF₂ (para)CF₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CHF₂ (meta) CF₂ PyridinylNH—C(O) Pyrimidinyl Z₁: CH₂—CHF₂ (ortho) CF₂ Pyridinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CF₃ (para) CF₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CF₃ (meta) CF₂ Pyridinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CF₃ (ortho) CF₂pyridinyl NH—C(O) Pyrazinyl None CF₂ pyridinyl NH—C(O) Pyrazinyl Z₁: F(para) CF₂ pyridinyl NH—C(O) Pyrazinyl Z₁: F (meta) CF₂ pyridinylNH—C(O) Pyrazinyl Z₁: F (ortho) CF₂ pyridinyl NH—C(O) Pyrazinyl Z₁: F(para) Z₂: F (meta) CF₂ Pyridinyl NH—C(O) Pyrazinyl Z₁: Cl (meta) CF₂Pyridinyl NH—C(O) Pyrazinyl Z₁: Cl (para) CF₂ Pyridinyl NH—C(O)Pyrazinyl Z₁: Cl (para) Z₂: Cl (meta) CF₂ Pyridinyl NH—C(O) PyrazinylZ₁: F (para) Z₂: Cl (meta) CF₂ Pyridinyl NH—C(O) Pyrazinyl Z₁: Cl (para)Z₂: F (meta) CF₂ Pyridinyl NH—C(O) Pyrazinyl Z₁: CH₃ (para) CF₂Pyridinyl NH—C(O) Pyrazinyl Z₁: CH₃ (meta) CF₂ Pyridinyl NH—C(O)Pyrazinyl Z₁: CH₃ (ortho) CF₂ Pyridinyl NH—C(O) Pyrazinyl Z₁: CH₂—CH₃(para) CF₂ Pyridinyl NH—C(O) Pyrazinyl Z₁: CH₂—CH₃ (meta) CF₂ PyridinylNH—C(O) Pyrazinyl Z₁: CH₂—CH₃ (ortho) CF₂ Pyridinyl NH—C(O) PyrazinylZ₁: CH₂—CH₂—CH₃ or iPr (para) CF₂ Pyridinyl NH—C(O) Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) CF₂ Pyridinyl NH—C(O) Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyridinyl NH—C(O) Pyrazinyl Z₁: CH₂F(para) CF₂ Pyridinyl NH—C(O) Pyrazinyl Z₁: CH₂F (meta) CF₂ PyridinylNH—C(O) Pyrazinyl Z₁: CH₂F (ortho) CF₂ Pyridinyl NH—C(O) Pyrazinyl Z₁:CHF₂ (para) CF₂ Pyridinyl NH—C(O) Pyrazinyl Z₁: CHF₂ (meta) CF₂Pyridinyl NH—C(O) Pyrazinyl Z₁: CHF₂ (ortho) CF₂ Pyridinyl NH—C(O)Pyrazinyl Z₁: CF₃ (para) CF₂ Pyridinyl NH—C(O) Pyrazinyl Z₁: CF₃ (meta)CF₂ Pyridinyl NH—C(O) Pyrazinyl Z₁: CF₃ (ortho) CF₂ Pyridinyl NH—C(O)Pyrazinyl Z₁: CH₂—CH₂F (para) CF₂ Pyridinyl NH—C(O) Pyrazinyl Z₁:CH₂—CH₂F (meta) CF₂ Pyridinyl NH—C(O) Pyrazinyl Z₁: CH₂—CH₂F (ortho) CF₂Pyridinyl NH—C(O) Pyrazinyl Z₁: CH₂—CHF₂ (para) CF₂ Pyridinyl NH—C(O)Pyrazinyl Z₁: CH₂—CHF₂ (meta) CF₂ Pyridinyl NH—C(O) Pyrazinyl Z₁:CH₂—CHF₂ (ortho) CF₂ Pyridinyl NH—C(O) Pyrazinyl Z₁: CH₂—CF₃ (para) CF₂Pyridinyl NH—C(O) Pyrazinyl Z₁: CH₂—CF₃ (meta) CF₂ Pyridinyl NH—C(O)Pyrazinyl Z₁: CH₂—CF₃ (ortho) CF₂ pyridinyl NH—C(O) Pyrrolyl None CF₂pyridinyl NH—C(O) Pyrrolyl Z₁: F (2) CF₂ pyridinyl NH—C(O) Pyrrolyl Z₁:F (3) CF₂ pyridinyl NH—C(O) Pyrrolyl Z₁: F (2) Z₂: F (3) CF₂ PyridinylNH—C(O) Pyrrolyl Z₁: Cl (2) CF₂ Pyridinyl NH—C(O) Pyrrolyl Z₁: Cl (3)CF₂ Pyridinyl NH—C(O) Pyrrolyl Z₁: Cl (2) Z₂: Cl (3) CF₂ PyridinylNH—C(O) Pyrrolyl Z₁: F (2) Z₂: Cl (3) CF₂ Pyridinyl NH—C(O) Pyrrolyl Z₁:Cl (2) Z₂: F (3) CF₂ Pyridinyl NH—C(O) Pyrrolyl Z₁: CH₃ (2) CF₂Pyridinyl NH—C(O) Pyrrolyl Z₁: CH₃ (3) CF₂ Pyridinyl NH—C(O) PyrrolylZ₁: CH₂—CH₃ (2) CF₂ Pyridinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₃ (3) CF₂Pyridinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂ PyridinylNH—C(O) Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CF₂ Pyridinyl NH—C(O)Pyrrolyl Z₁: CH₂F (2) CF₂ Pyridinyl NH—C(O) Pyrrolyl Z₁: CH₂F (3) CF₂Pyridinyl NH—C(O) Pyrrolyl Z₁: CHF₂ (2) CF₂ Pyridinyl NH—C(O) PyrrolylZ₁: CHF₂ (3) CF₂ Pyridinyl NH—C(O) Pyrrolyl Z₁: CF₃ (2) CF₂ PyridinylNH—C(O) Pyrrolyl Z₁: CF₃ (3) CF₂ Pyridinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₂F(2) CF₂ Pyridinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₂F (3) CF₂ PyridinylNH—C(O) Pyrrolyl Z₁: CH₂—CHF₂ (2) CF₂ Pyridinyl NH—C(O) Pyrrolyl Z₁:CH₂—CHF₂ (3) CF₂ Pyridinyl NH—C(O) Pyrrolyl Z₁: CH₂—CF₃ (2) CF₂Pyridinyl NH—C(O) Pyrrolyl Z₁: CH₂—CF₃ (3) CF₂ pyridinyl NH—C(O)Imidazolyl None CF₂ pyridinyl NH—C(O) Imidazolyl Z₁: F (2) CF₂ pyridinylNH—C(O) Imidazolyl Z₁: F (3) CF₂ pyridinyl NH—C(O) Imidazolyl Z₁: F (2)Z₂: F (3) CF₂ Pyridinyl NH—C(O) Imidazolyl Z₁: Cl (2) CF₂ PyridinylNH—C(O) Imidazolyl Z₁: Cl (3) CF₂ Pyridinyl NH—C(O) Imidazolyl Z₁: Cl(2) Z₂: Cl (3) CF₂ Pyridinyl NH—C(O) Imidazolyl Z₁: F (2) Z₂: Cl (3) CF₂Pyridinyl NH—C(O) Imidazolyl Z₁: Cl (2) Z₂: F (3) CF₂ Pyridinyl NH—C(O)Imidazolyl Z₁: CH₃ (2) CF₂ Pyridinyl NH—C(O) Imidazolyl Z₁: CH₃ (3) CF₂Pyridinyl NH—C(O) Imidazolyl Z₁: CH₂—CH₃ (2) CF₂ Pyridinyl NH—C(O)Imidazolyl Z₁: CH₂—CH₃ (3) CF₂ Pyridinyl NH—C(O) Imidazolyl Z₁:CH₂—CH₂—CH₃ or iPr (2) CF₂ Pyridinyl NH—C(O) Imidazolyl Z₁: CH₂—CH₂—CH₃or iPr (3) CF₂ Pyridinyl NH—C(O) Imidazolyl Z₁: CH₂F (2) CF₂ PyridinylNH—C(O) Imidazolyl Z₁: CH₂F (3) CF₂ Pyridinyl NH—C(O) Imidazolyl Z₁:CHF₂ (2) CF₂ Pyridinyl NH—C(O) Imidazolyl Z₁: CHF₂ (3) CF₂ PyridinylNH—C(O) Imidazolyl Z₁: CF₃ (2) CF₂ Pyridinyl NH—C(O) Imidazolyl Z₁: CF₃(3) CF₂ Pyridinyl NH—C(O) Imidazolyl Z₁: CH₂—CH₂F (2) CF₂ PyridinylNH—C(O) Imidazolyl Z₁: CH₂—CH₂F (3) CF₂ Pyridinyl NH—C(O) Imidazolyl Z₁:CH₂—CHF₂ (2) CF₂ Pyridinyl NH—C(O) Imidazolyl Z₁: CH₂—CHF₂ (3) CF₂Pyridinyl NH—C(O) Imidazolyl Z₁: CH₂—CF₃ (2) CF₂ Pyridinyl NH—C(O)Imidazolyl Z₁: CH₂—CF₃ (3) CF₂ pyridinyl NH—C(O) Furanyl None CF₂pyridinyl NH—C(O) Furanyl Z₁: F (2) CF₂ pyridinyl NH—C(O) Furanyl Z₁: F(3) CF₂ pyridinyl NH—C(O) Furanyl Z₁: F (2) Z₂: F (3) CF₂ PyridinylNH—C(O) Furanyl Z₁: Cl (2) CF₂ Pyridinyl NH—C(O) Furanyl Z₁: Cl (3) CF₂Pyridinyl NH—C(O) Furanyl Z₁: Cl (2) Z₂: Cl (3) CF₂ Pyridinyl NH—C(O)Furanyl Z₁: F (2) Z₂: Cl (3) CF₂ Pyridinyl NH—C(O) Furanyl Z₁: Cl (2)Z₂: F (3) CF₂ Pyridinyl NH—C(O) Furanyl Z₁: CH₃ (2) CF₂ PyridinylNH—C(O) Furanyl Z₁: CH₃ (3) CF₂ Pyridinyl NH—C(O) Furanyl Z₁: CH₂—CH₃(2) CF₂ Pyridinyl NH—C(O) Furanyl Z₁: CH₂—CH₃ (3) CF₂ Pyridinyl NH—C(O)Furanyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂ Pyridinyl NH—C(O) Furanyl Z₁:CH₂—CH₂—CH₃ or iPr (3) CF₂ Pyridinyl NH—C(O) Furanyl Z₁: CH₂F (2) CF₂Pyridinyl NH—C(O) Furanyl Z₁: CH₂F (3) CF₂ Pyridinyl NH—C(O) Furanyl Z₁:CHF₂ (2) CF₂ Pyridinyl NH—C(O) Furanyl Z₁: CHF₂ (3) CF₂ PyridinylNH—C(O) Furanyl Z₁: CF₃ (2) CF₂ Pyridinyl NH—C(O) Furanyl Z₁: CF₃ (3)CF₂ Pyridinyl NH—C(O) Furanyl Z₁: CH₂—CH₂F (2) CF₂ Pyridinyl NH—C(O)Furanyl Z₁: CH₂—CH₂F (3) CF₂ Pyridinyl NH—C(O) Furanyl Z₁: CH₂—CHF₂ (2)CF₂ Pyridinyl NH—C(O) Furanyl Z₁: CH₂—CHF₂ (3) CF₂ Pyridinyl NH—C(O)Furanyl Z₁: CH₂—CF₃ (2) CF₂ Pyridinyl NH—C(O) Furanyl Z₁: CH₂—CF₃ (3)CF₂ pyridinyl NH—C(O) Oxazolyl None CF₂ pyridinyl NH—C(O) Oxazolyl Z₁: F(2) CF₂ pyridinyl NH—C(O) Oxazolyl Z₁: F (3) CF₂ pyridinyl NH—C(O)Oxazolyl Z₁: F (2) Z₂: F (3) CF₂ Pyridinyl NH—C(O) Oxazolyl Z₁: Cl (2)CF₂ Pyridinyl NH—C(O) Oxazolyl Z₁: Cl (3) CF₂ Pyridinyl NH—C(O) OxazolylZ₁: Cl (2) Z₂: Cl (3) CF₂ Pyridinyl NH—C(O) Oxazolyl Z₁: F (2) Z₂: Cl(3) CF₂ Pyridinyl NH—C(O) Oxazolyl Z₁: Cl (2) Z₂: F (3) CF₂ PyridinylNH—C(O) Oxazolyl Z₁: CH₃ (2) CF₂ Pyridinyl NH—C(O) Oxazolyl Z₁: CH₃ (3)CF₂ Pyridinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₃ (2) CF₂ Pyridinyl NH—C(O)Oxazolyl Z₁: CH₂—CH₃ (3) CF₂ Pyridinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₂—CH₃or iPr (2) CF₂ Pyridinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CF₂Pyridinyl NH—C(O) Oxazolyl Z₁: CH₂F (2) CF₂ Pyridinyl NH—C(O) OxazolylZ₁: CH₂F (3) CF₂ Pyridinyl NH—C(O) Oxazolyl Z₁: CHF₂ (2) CF₂ PyridinylNH—C(O) Oxazolyl Z₁: CHF₂ (3) CF₂ Pyridinyl NH—C(O) Oxazolyl Z₁: CF₃ (2)CF₂ Pyridinyl NH—C(O) Oxazolyl Z₁: CF₃ (3) CF₂ Pyridinyl NH—C(O)Oxazolyl Z₁: CH₂—CH₂F (2) CF₂ Pyridinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₂F(3) CF₂ Pyridinyl NH—C(O) Oxazolyl Z₁: CH₂—CHF₂ (2) CF₂ PyridinylNH—C(O) Oxazolyl Z₁: CH₂—CHF₂ (3) CF₂ Pyridinyl NH—C(O) Oxazolyl Z₁:CH₂—CF₃ (2) CF₂ Pyridinyl NH—C(O) Oxazolyl Z₁: CH₂—CF₃ (3) CF₂ pyridinylNH—C(O) Thiophenyl None CF₂ pyridinyl NH—C(O) Thiophenyl Z₁: F (2) CF₂pyridinyl NH—C(O) Thiophenyl Z₁: F (3) CF₂ pyridinyl NH—C(O) ThiophenylZ₁: F (2) Z₂: F (3) CF₂ Pyridinyl NH—C(O) Thiophenyl Z₁: Cl (2) CF₂Pyridinyl NH—C(O) Thiophenyl Z₁: Cl (3) CF₂ Pyridinyl NH—C(O) ThiophenylZ₁: Cl (2) Z₂: Cl (3) CF₂ Pyridinyl NH—C(O) Thiophenyl Z₁: F (2) Z₂: Cl(3) CF₂ Pyridinyl NH—C(O) Thiophenyl Z₁: Cl (2) Z₂: F (3) CF₂ PyridinylNH—C(O) Thiophenyl Z₁: CH₃ (2) CF₂ Pyridinyl NH—C(O) Thiophenyl Z₁: CH₃(3) CF₂ Pyridinyl NH—C(O) Thiophenyl Z₁: CH₂—CH₃ (2) CF₂ PyridinylNH—C(O) Thiophenyl Z₁: CH₂—CH₃ (3) CF₂ Pyridinyl NH—C(O) Thiophenyl Z₁:CH₂—CH₂—CH₃ or iPr (2) CF₂ Pyridinyl NH—C(O) Thiophenyl Z₁: CH₂—CH₂—CH₃or iPr (3) CF₂ Pyridinyl NH—C(O) Thiophenyl Z₁: CH₂F (2) CF₂ PyridinylNH—C(O) Thiophenyl Z₁: CH₂F (3) CF₂ Pyridinyl NH—C(O) Thiophenyl Z₁:CHF₂ (2) CF₂ Pyridinyl NH—C(O) Thiophenyl Z₁: CHF₂ (3) CF₂ PyridinylNH—C(O) Thiophenyl Z₁: CF₃ (2) CF₂ Pyridinyl NH—C(O) Thiophenyl Z₁: CF₃(3) CF₂ Pyridinyl NH—C(O) Thiophenyl Z₁: CH₂—CH₂F (2) CF₂ PyridinylNH—C(O) Thiophenyl Z₁: CH₂—CH₂F (3) CF₂ Pyridinyl NH—C(O) Thiophenyl Z₁:CH₂—CHF₂ (2) CF₂ Pyridinyl NH—C(O) Thiophenyl Z₁: CH₂—CHF₂ (3) CF₂Pyridinyl NH—C(O) Thiophenyl Z₁: CH₂—CF₃ (2) CF₂ Pyridinyl NH—C(O)Thiophenyl Z₁: CH₂—CF₃ (3) CF₂ pyridinyl NH—C(O) Thiazolyl None CF₂pyridinyl NH—C(O) Thiazolyl Z₁: F (2) CF₂ pyridinyl NH—C(O) ThiazolylZ₁: F (3) CF₂ pyridinyl NH—C(O) Thiazolyl Z₁: F (2) Z₂: F (3) CF₂Pyridinyl NH—C(O) Thiazolyl Z₁: Cl (2) CF₂ Pyridinyl NH—C(O) ThiazolylZ₁: Cl (3) CF₂ Pyridinyl NH—C(O) Thiazolyl Z₁: Cl (2) Z₂: Cl (3) CF₂Pyridinyl NH—C(O) Thiazolyl Z₁: F (2) Z₂: Cl (3) CF₂ Pyridinyl NH—C(O)Thiazolyl Z₁: Cl (2) Z₂: F (3) CF₂ Pyridinyl NH—C(O) Thiazolyl Z₁: CH₃(2) CF₂ Pyridinyl NH—C(O) Thiazolyl Z₁: CH₃ (3) CF₂ Pyridinyl NH—C(O)Thiazolyl Z₁: CH₂—CH₃ (2) CF₂ Pyridinyl NH—C(O) Thiazolyl Z₁: CH₂—CH₃(3) CF₂ Pyridinyl NH—C(O) Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂Pyridinyl NH—C(O) Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CF₂ PyridinylNH—C(O) Thiazolyl Z₁: CH₂F (2) CF₂ Pyridinyl NH—C(O) Thiazolyl Z₁: CH₂F(3) CF₂ Pyridinyl NH—C(O) Thiazolyl Z₁: CHF₂ (2) CF₂ Pyridinyl NH—C(O)Thiazolyl Z₁: CHF₂ (3) CF₂ Pyridinyl NH—C(O) Thiazolyl Z₁: CF₃ (2) CF₂Pyridinyl NH—C(O) Thiazolyl Z₁: CF₃ (3) CF₂ Pyridinyl NH—C(O) ThiazolylZ₁: CH₂—CH₂F (2) CF₂ Pyridinyl NH—C(O) Thiazolyl Z₁: CH₂—CH₂F (3) CF₂Pyridinyl NH—C(O) Thiazolyl Z₁: CH₂—CHF₂ (2) CF₂ Pyridinyl NH—C(O)Thiazolyl Z₁: CH₂—CHF₂ (3) CF₂ Pyridinyl NH—C(O) Thiazolyl Z₁: CH₂—CF₃(2) CF₂ Pyridinyl NH—C(O) Thiazolyl Z₁: CH₂—CF₃ (3) CF₂ pyridinyl NH—SO₂Phenyl None CF₂ pyridinyl NH—SO₂ Phenyl Z₁: F (para) CF₂ pyridinylNH—SO₂ phenyl Z₁: F (meta) CF₂ pyridinyl NH—SO₂ phenyl Z₁: F (ortho) CF₂pyridinyl NH—SO₂ phenyl Z₁: F (para) Z₂: F (meta) CF₂ Pyridinyl NH—SO₂Phenyl Z₁: Cl (meta) CF₂ Pyridinyl NH—SO₂ Phenyl Z₁: Cl (para) CF₂Pyridinyl NH—SO₂ Phenyl Z₁: Cl (para) Z₂: Cl (meta) CF₂ Pyridinyl NH—SO₂Phenyl Z₁: F (para) Z₂: Cl (meta) CF₂ Pyridinyl NH—SO₂ Phenyl Z₁: Cl(para) Z₂: F (meta) CF₂ Pyridinyl NH—SO₂ Phenyl Z₁: CH₃ (para) CF₂Pyridinyl NH—SO₂ Phenyl Z₁: CH₃ (meta) CF₂ Pyridinyl NH—SO₂ Phenyl Z₁:CH₃ (ortho) CF₂ Pyridinyl NH—SO₂ Phenyl Z₁: CH₂—CH₃ (para) CF₂ PyridinylNH—SO₂ Phenyl Z₁: CH₂—CH₃ (meta) CF₂ Pyridinyl NH—SO₂ Phenyl Z₁: CH₂—CH₃(ortho) CF₂ Pyridinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CF₂Pyridinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CF₂ PyridinylNH—SO₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyridinyl NH—SO₂ PhenylZ₁: CH₂F (para) CF₂ Pyridinyl NH—SO₂ Phenyl Z₁: CH₂F (meta) CF₂Pyridinyl NH—SO₂ Phenyl Z₁: CH₂F (ortho) CF₂ Pyridinyl NH—SO₂ Phenyl Z₁:CHF₂ (para) CF₂ Pyridinyl NH—SO₂ Phenyl Z₁: CHF₂ (meta) CF₂ PyridinylNH—SO₂ Phenyl Z₁: CHF₂ (ortho) CF₂ Pyridinyl NH—SO₂ Phenyl Z₁: CF₃(para) CF₂ Pyridinyl NH—SO₂ Phenyl Z₁: CF₃ (meta) CF₂ Pyridinyl NH—SO₂Phenyl Z₁: CF₃ (ortho) CF₂ Pyridinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂F (para)CF₂ Pyridinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂F (meta) CF₂ Pyridinyl NH—SO₂Phenyl Z₁: CH₂—CH₂F (ortho) CF₂ Pyridinyl NH—SO₂ Phenyl Z₁: CH₂—CHF₂(para) CF₂ Pyridinyl NH—SO₂ Phenyl Z₁: CH₂—CHF₂ (meta) CF₂ PyridinylNH—SO₂ Phenyl Z₁: CH₂—CHF₂ (ortho) CF₂ Pyridinyl NH—SO₂ Phenyl Z₁:CH₂—CF₃ (para) CF₂ Pyridinyl NH—SO₂ Phenyl Z₁: CH₂—CF₃ (meta) CF₂Pyridinyl NH—SO₂ Phenyl Z₁: CH₂—CF₃ (ortho) CF₂ pyridinyl NH—SO₂Pyridinyl None CF₂ pyridinyl NH—SO₂ Pyridinyl Z₁: F (para) CF₂ pyridinylNH—SO₂ Pyridinyl Z₁: F (meta) CF₂ pyridinyl NH—SO₂ Pyridinyl Z₁: F(ortho) CF₂ pyridinyl NH—SO₂ Pyridinyl Z₁: F (para) Z₂: F (meta) CF₂Pyridinyl NH—SO₂ Pyridinyl Z₁: Cl (meta) CF₂ Pyridinyl NH—SO₂ PyridinylZ₁: Cl (para) CF₂ Pyridinyl NH—SO₂ Pyridinyl Z₁: Cl (para) Z₂: Cl (meta)CF₂ Pyridinyl NH—SO₂ Pyridinyl Z₁: F (para) Z₂: Cl (meta) CF₂ PyridinylNH—SO₂ Pyridinyl Z₁: Cl (para) Z₂: F (meta) CF₂ Pyridinyl NH—SO₂Pyridinyl Z₁: CH₃ (para) CF₂ Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₃ (meta)CF₂ Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₃ (ortho) CF₂ Pyridinyl NH—SO₂Pyridinyl Z₁: CH₂—CH₃ (para) CF₂ Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₃(meta) CF₂ Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₃ (ortho) CF₂ PyridinylNH—SO₂ Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CF₂ Pyridinyl NH—SO₂Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CF₂ Pyridinyl NH—SO₂ PyridinylZ₁: CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₂F(para) CF₂ Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₂F (meta) CF₂ PyridinylNH—SO₂ Pyridinyl Z₁: CH₂F (ortho) CF₂ Pyridinyl NH—SO₂ Pyridinyl Z₁:CHF₂ (para) CF₂ Pyridinyl NH—SO₂ Pyridinyl Z₁: CHF₂ (meta) CF₂ PyridinylNH—SO₂ Pyridinyl Z₁: CHF₂ (ortho) CF₂ Pyridinyl NH—SO₂ Pyridinyl Z₁: CF₃(para) CF₂ Pyridinyl NH—SO₂ Pyridinyl Z₁: CF₃ (meta) CF₂ PyridinylNH—SO₂ Pyridinyl Z₁: CF₃ (ortho) CF₂ Pyridinyl NH—SO₂ Pyridinyl Z₁:CH₂—CH₂F (para) CF₂ Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₂F (meta) CF₂Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₂F (ortho) CF₂ Pyridinyl NH—SO₂Pyridinyl Z₁: CH₂—CHF₂ (para) CF₂ Pyridinyl NH—SO₂ Pyridinyl Z₁:CH₂—CHF₂ (meta) CF₂ Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₂—CHF₂ (ortho) CF₂Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₂—CF₃ (para) CF₂ Pyridinyl NH—SO₂Pyridinyl Z₁: CH₂—CF₃ (meta) CF₂ Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₂—CF₃(ortho) CF₂ pyridinyl NH—SO₂ Pyrimidinyl None CF₂ pyridinyl NH—SO₂Pyrimidinyl Z₁: F (para) CF₂ pyridinyl NH—SO₂ Pyrimidinyl Z₁: F (meta)CF₂ pyridinyl NH—SO₂ Pyrimidinyl Z₁: F (ortho) CF₂ pyridinyl NH—SO₂Pyrimidinyl Z₁: F (para) Z₂: F (meta) CF₂ Pyridinyl NH—SO₂ PyrimidinylZ₁: Cl (meta) CF₂ Pyridinyl NH—SO₂ Pyrimidinyl Z₁: Cl (para) CF₂Pyridinyl NH—SO₂ Pyrimidinyl Z₁: Cl (para) Z₂: Cl (meta) CF₂ PyridinylNH—SO₂ Pyrimidinyl Z₁: F (para) Z₂: Cl (meta) CF₂ Pyridinyl NH—SO₂Pyrimidinyl Z₁: Cl (para) Z₂: F (meta) CF₂ Pyridinyl NH—SO₂ PyrimidinylZ₁: CH₃ (para) CF₂ Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₃ (meta) CF₂Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₃ (ortho) CF₂ Pyridinyl NH—SO₂Pyrimidinyl Z₁: CH₂—CH₃ (para) CF₂ Pyridinyl NH—SO₂ Pyrimidinyl Z₁:CH₂—CH₃ (meta) CF₂ Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₃ (ortho) CF₂Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CF₂ PyridinylNH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CF₂ Pyridinyl NH—SO₂Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyridinyl NH—SO₂Pyrimidinyl Z₁: CH₂F (para) CF₂ Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₂F(meta) CF₂ Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₂F (ortho) CF₂ PyridinylNH—SO₂ Pyrimidinyl Z₁: CHF₂ (para) CF₂ Pyridinyl NH—SO₂ Pyrimidinyl Z₁:CHF₂ (meta) CF₂ Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CHF₂ (ortho) CF₂Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CF₃ (para) CF₂ Pyridinyl NH—SO₂Pyrimidinyl Z₁: CF₃ (meta) CF₂ Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CF₃(ortho) CF₂ Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂F (para) CF₂Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂F (meta) CF₂ Pyridinyl NH—SO₂Pyrimidinyl Z₁: CH₂—CH₂F (ortho) CF₂ Pyridinyl NH—SO₂ Pyrimidinyl Z₁:CH₂—CHF₂ (para) CF₂ Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CHF₂ (meta) CF₂Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CHF₂ (ortho) CF₂ Pyridinyl NH—SO₂Pyrimidinyl Z₁: CH₂—CF₃ (para) CF₂ Pyridinyl NH—SO₂ Pyrimidinyl Z₁:CH₂—CF₃ (meta) CF₂ Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CF₃ (ortho) CF₂pyridinyl NH—SO₂ Pyrazinyl None CF₂ pyridinyl NH—SO₂ Pyrazinyl Z₁: F(para) CF₂ pyridinyl NH—SO₂ Pyrazinyl Z₁: F (meta) CF₂ pyridinyl NH—SO₂Pyrazinyl Z₁: F (ortho) CF₂ pyridinyl NH—SO₂ Pyrazinyl Z₁: F (para) Z₂:F (meta) CF₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: Cl (meta) CF₂ PyridinylNH—SO₂ Pyrazinyl Z₁: Cl (para) CF₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: Cl(para) Z₂: Cl (meta) CF₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: F (para) Z₂: Cl(meta) CF₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: Cl (para) Z₂: F (meta) CF₂Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₃ (para) CF₂ Pyridinyl NH—SO₂ PyrazinylZ₁: CH₃ (meta) CF₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₃ (ortho) CF₂Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₃ (para) CF₂ Pyridinyl NH—SO₂Pyrazinyl Z₁: CH₂—CH₃ (meta) CF₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₃(ortho) CF₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CF₂Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CF₂ PyridinylNH—SO₂ Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyridinyl NH—SO₂Pyrazinyl Z₁: CH₂F (para) CF₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₂F (meta)CF₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₂F (ortho) CF₂ Pyridinyl NH—SO₂Pyrazinyl Z₁: CHF₂ (para) CF₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: CHF₂ (meta)CF₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: CHF₂ (ortho) CF₂ Pyridinyl NH—SO₂Pyrazinyl Z₁: CF₃ (para) CF₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: CF₃ (meta)CF₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: CF₃ (ortho) CF₂ Pyridinyl NH—SO₂Pyrazinyl Z₁: CH₂—CH₂F (para) CF₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁:CH₂—CH₂F (meta) CF₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₂F (ortho) CF₂Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CHF₂ (para) CF₂ Pyridinyl NH—SO₂Pyrazinyl Z₁: CH₂—CHF₂ (meta) CF₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁:CH₂—CHF₂ (ortho) CF₂ Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CF₃ (para) CF₂Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CF₃ (meta) CF₂ Pyridinyl NH—SO₂Pyrazinyl Z₁: CH₂—CF₃ (ortho) CF₂ pyridinyl NH—SO₂ Pyrrolyl None CF₂pyridinyl NH—SO₂ Pyrrolyl Z₁: F (2) CF₂ pyridinyl NH—SO₂ Pyrrolyl Z₁: F(3) CF₂ pyridinyl NH—SO₂ Pyrrolyl Z₁: F (2) Z₂: F (3) CF₂ PyridinylNH—SO₂ Pyrrolyl Z₁: Cl (2) CF₂ Pyridinyl NH—SO₂ Pyrrolyl Z₁: Cl (3) CF₂Pyridinyl NH—SO₂ Pyrrolyl Z₁: Cl (2) Z₂: Cl (3) CF₂ Pyridinyl NH—SO₂Pyrrolyl Z₁: F (2) Z₂: Cl (3) CF₂ Pyridinyl NH—SO₂ Pyrrolyl Z₁: Cl (2)Z₂: F (3) CF₂ Pyridinyl NH—SO₂ Pyrrolyl Z₁: CH₃ (2) CF₂ Pyridinyl NH—SO₂Pyrrolyl Z₁: CH₃ (3) CF₂ Pyridinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CH₃ (2) CF₂Pyridinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CH₃ (3) CF₂ Pyridinyl NH—SO₂ PyrrolylZ₁: CH₂—CH₂—CH₃ or iPr (2) CF₂ Pyridinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CH₂—CH₃or iPr (3) CF₂ Pyridinyl NH—SO₂ Pyrrolyl Z₁: CH₂F (2) CF₂ PyridinylNH—SO₂ Pyrrolyl Z₁: CH₂F (3) CF₂ Pyridinyl NH—SO₂ Pyrrolyl Z₁: CHF₂ (2)CF₂ Pyridinyl NH—SO₂ Pyrrolyl Z₁: CHF₂ (3) CF₂ Pyridinyl NH—SO₂ PyrrolylZ₁: CF₃ (2) CF₂ Pyridinyl NH—SO₂ Pyrrolyl Z₁: CF₃ (3) CF₂ PyridinylNH—SO₂ Pyrrolyl Z₁: CH₂—CH₂F (2) CF₂ Pyridinyl NH—SO₂ Pyrrolyl Z₁:CH₂—CH₂F (3) CF₂ Pyridinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CHF₂ (2) CF₂Pyridinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CHF₂ (3) CF₂ Pyridinyl NH—SO₂ PyrrolylZ₁: CH₂—CF₃ (2) CF₂ Pyridinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CF₃ (3) CF₂pyridinyl NH—SO₂ Imidazolyl None CF₂ pyridinyl NH—SO₂ Imidazolyl Z₁: F(2) CF₂ pyridinyl NH—SO₂ Imidazolyl Z₁: F (3) CF₂ pyridinyl NH—SO₂Imidazolyl Z₁: F (2) Z₂: F (3) CF₂ Pyridinyl NH—SO₂ Imidazolyl Z₁: Cl(2) CF₂ Pyridinyl NH—SO₂ Imidazolyl Z₁: Cl (3) CF₂ Pyridinyl NH—SO₂Imidazolyl Z₁: Cl (2) Z₂: Cl (3) CF₂ Pyridinyl NH—SO₂ Imidazolyl Z₁: F(2) Z₂: Cl (3) CF₂ Pyridinyl NH—SO₂ Imidazolyl Z₁: Cl (2) Z₂: F (3) CF₂Pyridinyl NH—SO₂ Imidazolyl Z₁: CH₃ (2) CF₂ Pyridinyl NH—SO₂ ImidazolylZ₁: CH₃ (3) CF₂ Pyridinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₃ (2) CF₂Pyridinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₃ (3) CF₂ Pyridinyl NH—SO₂Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂ Pyridinyl NH—SO₂ ImidazolylZ₁: CH₂—CH₂—CH₃ or iPr (3) CF₂ Pyridinyl NH—SO₂ Imidazolyl Z₁: CH₂F (2)CF₂ Pyridinyl NH—SO₂ Imidazolyl Z₁: CH₂F (3) CF₂ Pyridinyl NH—SO₂Imidazolyl Z₁: CHF₂ (2) CF₂ Pyridinyl NH—SO₂ Imidazolyl Z₁: CHF₂ (3) CF₂Pyridinyl NH—SO₂ Imidazolyl Z₁: CF₃ (2) CF₂ Pyridinyl NH—SO₂ ImidazolylZ₁: CF₃ (3) CF₂ Pyridinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₂F (2) CF₂Pyridinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₂F (3) CF₂ Pyridinyl NH—SO₂Imidazolyl Z₁: CH₂—CHF₂ (2) CF₂ Pyridinyl NH—SO₂ Imidazolyl Z₁: CH₂—CHF₂(3) CF₂ Pyridinyl NH—SO₂ Imidazolyl Z₁: CH₂—CF₃ (2) CF₂ Pyridinyl NH—SO₂Imidazolyl Z₁: CH₂—CF₃ (3) CF₂ pyridinyl NH—SO₂ Furanyl None CF₂pyridinyl NH—SO₂ Furanyl Z₁: F (2) CF₂ pyridinyl NH—SO₂ Furanyl Z₁: F(3) CF₂ pyridinyl NH—SO₂ Furanyl Z₁: F (2) Z₂: F (3) CF₂ PyridinylNH—SO₂ Furanyl Z₁: Cl (2) CF₂ Pyridinyl NH—SO₂ Furanyl Z₁: Cl (3) CF₂Pyridinyl NH—SO₂ Furanyl Z₁: Cl (2) Z₂: Cl (3) CF₂ Pyridinyl NH—SO₂Furanyl Z₁: F (2) Z₁: Cl (3) CF₂ Pyridinyl NH—SO₂ Furanyl Z₁: Cl (2) Z₂:F (3) CF₂ Pyridinyl NH—SO₂ Furanyl Z₁: CH₃ (2) CF₂ Pyridinyl NH—SO₂Furanyl Z₁: CH₃ (3) CF₂ Pyridinyl NH—SO₂ Furanyl Z₁: CH₂—CH₃ (2) CF₂Pyridinyl NH—SO₂ Furanyl Z₁: CH₂—CH₃ (3) CF₂ Pyridinyl NH—SO₂ FuranylZ₁: CH₂—CH₂—CH₃ or iPr (2) CF₂ Pyridinyl NH—SO₂ Furanyl Z₁: CH₂—CH₂—CH₃or iPr (3) CF₂ Pyridinyl NH—SO₂ Furanyl Z₁: CH₂F (2) CF₂ PyridinylNH—SO₂ Furanyl Z₁: CH₂F (3) CF₂ Pyridinyl NH—SO₂ Furanyl Z₁: CHF₂ (2)CF₂ Pyridinyl NH—SO₂ Furanyl Z₁: CHF₂ (3) CF₂ Pyridinyl NH—SO₂ FuranylZ₁: CF₃ (2) CF₂ Pyridinyl NH—SO₂ Furanyl Z₁: CF₃ (3) CF₂ PyridinylNH—SO₂ Furanyl Z₁: CH₂—CH₂F (2) CF₂ Pyridinyl NH—SO₂ Furanyl Z₁:CH₂—CH₂F (3) CF₂ Pyridinyl NH—SO₂ Furanyl Z₁: CH₂—CHF₂ (2) CF₂ PyridinylNH—SO₂ Furanyl Z₁: CH₂—CHF₂ (3) CF₂ Pyridinyl NH—SO₂ Furanyl Z₁: CH₂—CF₃(2) CF₂ Pyridinyl NH—SO₂ Furanyl Z₁: CH₂—CF₃ (3) CF₂ pyridinyl NH—SO₂Oxazolyl None CF₂ pyridinyl NH—SO₂ Oxazolyl Z₁: F (2) CF₂ pyridinylNH—SO₂ Oxazolyl Z₁: F (3) CF₂ pyridinyl NH—SO₂ Oxazolyl Z₁: F (2) Z₂: F(3) CF₂ Pyridinyl NH—SO₂ Oxazolyl Z₁: Cl (2) CF₂ Pyridinyl NH—SO₂Oxazolyl Z₁: Cl (3) CF₂ Pyridinyl NH—SO₂ Oxazolyl Z₁: Cl (2) Z₂: Cl (3)CF₂ Pyridinyl NH—SO₂ Oxazolyl Z₁: F (2) Z₂: Cl (3) CF₂ Pyridinyl NH—SO₂Oxazolyl Z₁: Cl (2) Z₂: F (3) CF₂ Pyridinyl NH—SO₂ Oxazolyl Z₁: CH₃ (2)CF₂ Pyridinyl NH—SO₂ Oxazolyl Z₁: CH₃ (3) CF₂ Pyridinyl NH—SO₂ OxazolylZ₁: CH₂—CH₃ (2) CF₂ Pyridinyl NH—SO₂ Oxazolyl Z₁: CH₂—CH₃ (3) CF₂Pyridinyl NH—SO₂ Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂ PyridinylNH—SO₂ Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CF₂ Pyridinyl NH—SO₂ OxazolylZ₁: CH₂F (2) CF₂ Pyridinyl NH—SO₂ Oxazolyl Z₁: CH₂F (3) CF₂ PyridinylNH—SO₂ Oxazolyl Z₁: CHF₂ (2) CF₂ Pyridinyl NH—SO₂ Oxazolyl Z₁: CHF₂ (3)CF₂ Pyridinyl NH—SO₂ Oxazolyl Z₁: CF₃ (2) CF₂ Pyridinyl NH—SO₂ OxazolylZ₁: CF₃ (3) CF₂ Pyridinyl NH—SO₂ Oxazolyl Z₁: CH₂—CH₂F (2) CF₂ PyridinylNH—SO₂ Oxazolyl Z₁: CH₂—CH₂F (3) CF₂ Pyridinyl NH—SO₂ Oxazolyl Z₁:CH₂—CHF₂ (2) CF₂ Pyridinyl NH—SO₂ Oxazolyl Z₁: CH₂—CHF₂ (3) CF₂Pyridinyl NH—SO₂ Oxazolyl Z₁: CH₂—CF₃ (2) CF₂ Pyridinyl NH—SO₂ OxazolylZ₁: CH₂—CF₃ (3) CF₂ pyridinyl NH—SO₂ Thiophenyl None CF₂ pyridinylNH—SO₂ Thiophenyl Z₁: F (2) CF₂ pyridinyl NH—SO₂ Thiophenyl Z₁: F (3)CF₂ pyridinyl NH—SO₂ Thiophenyl Z₁: F (2) Z₂: F (3) CF₂ Pyridinyl NH—SO₂Thiophenyl Z₁: Cl (2) CF₂ Pyridinyl NH—SO₂ Thiophenyl Z₁: Cl (3) CF₂Pyridinyl NH—SO₂ Thiophenyl Z₁: Cl (2) Z₂: Cl (3) CF₂ Pyridinyl NH—SO₂Thiophenyl Z₁: F (2) Z₂: Cl (3) CF₂ Pyridinyl NH—SO₂ Thiophenyl Z₁: Cl(2) Z₂: F (3) CF₂ Pyridinyl NH—SO₂ Thiophenyl Z₁: CH₃ (2) CF₂ PyridinylNH—SO₂ Thiophenyl Z₁: CH₃ (3) CF₂ Pyridinyl NH—SO₂ Thiophenyl Z₁:CH₂—CH₃ (2) CF₂ Pyridinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₃ (3) CF₂Pyridinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂ PyridinylNH—SO₂ Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CF₂ Pyridinyl NH—SO₂Thiophenyl Z₁: CH₂F (2) CF₂ Pyridinyl NH—SO₂ Thiophenyl Z₁: CH₂F (3) CF₂Pyridinyl NH—SO₂ Thiophenyl Z₁: CHF₂ (2) CF₂ Pyridinyl NH—SO₂ ThiophenylZ₁: CHF₂ (3) CF₂ Pyridinyl NH—SO₂ Thiophenyl Z₁: CF₃ (2) CF₂ PyridinylNH—SO₂ Thiophenyl Z₁: CF₃ (3) CF₂ Pyridinyl NH—SO₂ Thiophenyl Z₁:CH₂—CH₂F (2) CF₂ Pyridinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₂F (3) CF₂Pyridinyl NH—SO₂ Thiophenyl Z₁: CH₂—CHF₂ (2) CF₂ Pyridinyl NH—SO₂Thiophenyl Z₁: CH₂—CHF₂ (3) CF₂ Pyridinyl NH—SO₂ Thiophenyl Z₁: CH₂—CF₃(2) CF₂ Pyridinyl NH—SO₂ Thiophenyl Z₁: CH₂—CF₃ (3) CF₂ pyridinyl NH—SO₂Thiazolyl None CF₂ pyridinyl NH—SO₂ Thiazolyl Z₁: F (2) CF₂ pyridinylNH—SO₂ Thiazolyl Z₁: F (3) CF₂ pyridinyl NH—SO₂ Thiazolyl Z₁: F (2) Z₂:F (3) CF₂ Pyridinyl NH—SO₂ Thiazolyl Z₁: Cl (2) CF₂ Pyridinyl NH—SO₂Thiazolyl Z₁: Cl (3) CF₂ Pyridinyl NH—SO₂ Thiazolyl Z₁: Cl (2) Z₂: Cl(3) CF₂ Pyridinyl NH—SO₂ Thiazolyl Z₁: F (2) Z₂: Cl (3) CF₂ PyridinylNH—SO₂ Thiazolyl Z₁: Cl (2) Z₂: F (3) CF₂ Pyridinyl NH—SO₂ Thiazolyl Z₁:CH₃ (2) CF₂ Pyridinyl NH—SO₂ Thiazolyl Z₁: CH₃ (3) CF₂ Pyridinyl NH—SO₂Thiazolyl Z₁: CH₂—CH₃ (2) CF₂ Pyridinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₃ (3)CF₂ Pyridinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂ PyridinylNH—SO₂ Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CF₂ Pyridinyl NH—SO₂Thiazolyl Z₁: CH₂F (2) CF₂ Pyridinyl NH—SO₂ Thiazolyl Z₁: CH₂F (3) CF₂Pyridinyl NH—SO₂ Thiazolyl Z₁: CHF₂ (2) CF₂ Pyridinyl NH—SO₂ ThiazolylZ₁: CHF₂ (3) CF₂ Pyridinyl NH—SO₂ Thiazolyl Z₁: CF₃ (2) CF₂ PyridinylNH—SO₂ Thiazolyl Z₁: CF₃ (3) CF₂ Pyridinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₂F(2) CF₂ Pyridinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₂F (3) CF₂ Pyridinyl NH—SO₂Thiazolyl Z₁: CH₂—CHF₂ (2) CF₂ Pyridinyl NH—SO₂ Thiazolyl Z₁: CH₂—CHF₂(3) CF₂ Pyridinyl NH—SO₂ Thiazolyl Z₁: CH₂—CF₃ (2) CF₂ Pyridinyl NH—SO₂Thiazolyl Z₁: CH₂—CF₃ (3) CF₂ Pyrimidinyl NH—CH₂ Phenyl None CF₂Pyrimidinyl NH—CH₂ Phenyl Z₁: F (para) CF₂ Pyrimidinyl NH—CH₂ phenyl Z₁:F (meta) CF₂ Pyrimidinyl NH—CH₂ phenyl Z₁: F (ortho) CF₂ PyrimidinylNH—CH₂ phenyl Z₁: F (para) Z₂: F (meta) CF₂ Pyrimidinyl NH—CH₂ PhenylZ₁: Cl (meta) CF₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: Cl (para) CF₂Pyrimidinyl NH—CH₂ Phenyl Z₁: Cl (para) Z₂: Cl (meta) CF₂ PyrimidinylNH—CH₂ Phenyl Z₁: F (para) Z₂: Cl (meta) CF₂ Pyrimidinyl NH—CH₂ PhenylZ₁: Cl (para) Z₂: F (meta) CF₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₃ (para)CF₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₃ (meta) CF₂ Pyrimidinyl NH—CH₂Phenyl Z₁: CH₃ (ortho) CF₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CH₃ (para)CF₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CH₃ (meta) CF₂ Pyrimidinyl NH—CH₂Phenyl Z₁: CH₂—CH₃ (ortho) CF₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂—CH₃or iPr (para) CF₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr(meta) CF₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) CF₂Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂F (para) CF₂ Pyrimidinyl NH—CH₂ PhenylZ₁: CH₂F (meta) CF₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂F (ortho) CF₂Pyrimidinyl NH—CH₂ Phenyl Z₁: CHF₂ (para) CF₂ Pyrimidinyl NH—CH₂ PhenylZ₁: CHF₂ (meta) CF₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: CHF₂ (ortho) CF₂Pyrimidinyl NH—CH₂ Phenyl Z₁: CF₃ (para) CF₂ Pyrimidinyl NH—CH₂ PhenylZ₁: CF₃ (meta) CF₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: CF₃ (ortho) CF₂Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂F (para) CF₂ Pyrimidinyl NH—CH₂Phenyl Z₁: CH₂—CH₂F (meta) CF₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂F(ortho) CF₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CHF₂ (para) CF₂Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CHF₂ (meta) CF₂ Pyrimidinyl NH—CH₂Phenyl Z₁: CH₂—CHF₂ (ortho) CF₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CF₃(para) CF₂ Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CF₃ (meta) CF₂ PyrimidinylNH—CH₂ Phenyl Z₁: CH₂—CF₃ (ortho) CF₂ Pyrimidinyl NH—CH₂ Pyridinyl NoneCF₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: F (para) CF₂ Pyrimidinyl NH—CH₂Pyridinyl Z₁: F (meta) CF₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: F (ortho)CF₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: F (para) Z₂: F (meta) CF₂Pyrimidinyl NH—CH₂ Pyridinyl Z₁: Cl (meta) CF₂ Pyrimidinyl NH—CH₂Pyridinyl Z₁: Cl (para) CF₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: Cl (para)Z₂: Cl (meta) CF₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: F (para) Z₂: Cl(meta) CF₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: Cl (para) Z₂: F (meta) CF₂Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₃ (para) CF₂ Pyrimidinyl NH—CH₂Pyridinyl Z₁: CH₃ (meta) CF₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₃(ortho) CF₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₃ (para) CF₂Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₃ (meta) CF₂ Pyrimidinyl NH—CH₂Pyridinyl Z₁: CH₂—CH₃ (ortho) CF₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁:CH₂—CH₂—CH₃ or iPr (para) CF₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) CF₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₂F(para) CF₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₂F (meta) CF₂ PyrimidinylNH—CH₂ Pyridinyl Z₁: CH₂F (ortho) CF₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁:CHF₂ (para) CF₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CHF₂ (meta) CF₂Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CHF₂ (ortho) CF₂ Pyrimidinyl NH—CH₂Pyridinyl Z₁: CF₃ (para) CF₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CF₃ (meta)CF₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CF₃ (ortho) CF₂ Pyrimidinyl NH—CH₂Pyridinyl Z₁: CH₂—CH₂F (para) CF₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁:CH₂—CH₂F (meta) CF₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₂F (ortho)CF₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₂—CHF₂ (para) CF₂ PyrimidinylNH—CH₂ Pyridinyl Z₁: CH₂—CHF₂ (meta) CF₂ Pyrimidinyl NH—CH₂ PyridinylZ₁: CH₂—CHF₂ (ortho) CF₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₂—CF₃ (para)CF₂ Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₂—CF₃ (meta) CF₂ PyrimidinylNH—CH₂ Pyridinyl Z₁: CH₂—CF₃ (ortho) CF₂ Pyrimidinyl NH—CH₂ PyrimidinylNone CF₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: F (para) CF₂ PyrimidinylNH—CH₂ Pyrimidinyl Z₁: F (meta) CF₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: F(ortho) CF₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: F (para) Z₂: F (meta) CF₂Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: Cl (meta) CF₂ Pyrimidinyl NH—CH₂Pyrimidinyl Z₁: Cl (para) CF₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: Cl(para) Z₂: Cl (meta) CF₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: F (para) Z₂:Cl (meta) CF₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: Cl (para) Z₂: F (meta)CF₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₃ (para) CF₂ Pyrimidinyl NH—CH₂Pyrimidinyl Z₁: CH₃ (meta) CF₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₃(ortho) CF₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₃ (pam) CF₂Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₃ (meta) CF₂ Pyrimidinyl NH—CH₂Pyrimidinyl Z₁: CH₂—CH₃ (ortho) CF₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (para) CF₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) CF₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₂F(para) CF₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₂F (meta) CF₂Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₂F (ortho) CF₂ Pyrimidinyl NH—CH₂Pyrimidinyl Z₁: CHF₂ (para) CF₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CHF₂(meta) CF₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CHF₂ (ortho) CF₂Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CF₃ (para) CF₂ Pyrimidinyl NH—CH₂Pyrimidinyl Z₁: CF₃ (meta) CF₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CF₃(ortho) CF₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₂F (para) CF₂Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₂F (meta) CF₂ PyrimidinylNH—CH₂ Pyrimidinyl Z₁: CH₂—CH₂F (ortho) CF₂ Pyrimidinyl NH—CH₂Pyrimidinyl Z₁: CH₂—CHF₂ (para) CF₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁:CH₂—CHF₂ (meta) CF₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CHF₂ (ortho)CF₂ Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CF₃ (para) CF₂ PyrimidinylNH—CH₂ Pyrimidinyl Z₁: CH₂—CF₃ (meta) CF₂ Pyrimidinyl NH—CH₂ PyrimidinylZ₁: CH₂—CF₃ (ortho) CF₂ Pyrimidinyl NH—CH₂ Pyrazinyl None CF₂Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: F (para) CF₂ Pyrimidinyl NH—CH₂Pyrazinyl Z₁: F (meta) CF₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: F (ortho)CF₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: F (para) Z₂: F (meta) CF₂Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: Cl (meta) CF₂ Pyrimidinyl NH—CH₂Pyrazinyl Z₁: Cl (para) CF₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: Cl (para)Z₂: Cl (meta) CF₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: F (para) Z₂: Cl(meta) CF₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: Cl (para) Z₂: F (meta) CF₂Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₃ (para) CF₂ Pyrimidinyl NH—CH₂Pyrazinyl Z₁: CH₃ (meta) CF₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₃(ortho) CF₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₃ (para) CF₂Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₃ (meta) CF₂ Pyrimidinyl NH—CH₂Pyrazinyl Z₁: CH₂—CH₃ (ortho) CF₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (para) CF₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) CF₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₂F(para) CF₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₂F (meta) CF₂ PyrimidinylNH—CH₂ Pyrazinyl Z₁: CH₂F (ortho) CF₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁:CHF₂ (para) CF₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CHF₂ (meta) CF₂Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CHF₂ (ortho) CF₂ Pyrimidinyl NH—CH₂Pyrazinyl Z₁: CF₃ (para) CF₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CF₃ (meta)CF₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CF₃ (ortho) CF₂ Pyrimidinyl NH—CH₂Pyrazinyl Z₁: CH₂—CH₂F (para) CF₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁:CH₂—CH₂F (meta) CF₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₂F (ortho)CF₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CHF₂ (para) CF₂ PyrimidinylNH—CH₂ Pyrazinyl Z₁: CH₂—CHF₂ (meta) CF₂ Pyrimidinyl NH—CH₂ PyrazinylZ₁: CH₂—CHF₂ (ortho) CF₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CF₃ (para)CF₂ Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CF₃ (meta) CF₂ PyrimidinylNH—CH₂ Pyrazinyl Z₁: CH₂—CF₃ (ortho) CF₂ Pyrimidinyl NH—CH₂ PyrrolylNone CF₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: F (2) CF₂ Pyrimidinyl NH—CH₂Pyrrolyl Z₁: F (3) CF₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: F (2) Z₂: F (3)CF₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: Cl (2) CF₂ Pyrimidinyl NH—CH₂Pyrrolyl Z₁: Cl (3) CF₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: Cl (2) Z₂: Cl(3) CF₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: F (2) Z₂: Cl (3) CF₂ PyrimidinylNH—CH₂ Pyrrolyl Z₁: Cl (2) Z₂: F (3) CF₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁:CH₃ (2) CF₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: CH₃ (3) CF₂ PyrimidinylNH—CH₂ Pyrrolyl Z₁: CH₂—CH₃ (2) CF₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁:CH₂—CH₃ (3) CF₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (2)CF₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CF₂Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: CH₂F (2) CF₂ Pyrimidinyl NH—CH₂ PyrrolylZ₁: CH₂F (3) CF₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: CHF₂ (2) CF₂Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: CHF₂ (3) CF₂ Pyrimidinyl NH—CH₂ PyrrolylZ₁: CF₃ (2) CF₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: CF₃ (3) CF₂ PyrimidinylNH—CH₂ Pyrrolyl Z₁: CH₂—CH₂F (2) CF₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁:CH₂—CH₂F (3) CF₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CHF₂ (2) CF₂Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CHF₂ (3) CF₂ Pyrimidinyl NH—CH₂Pyrrolyl Z₁: CH₂—CF₃ (2) CF₂ Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CF₃ (3)CF₂ Pyrimidinyl NH—CH₂ Imidazolyl None CF₂ Pyrimidinyl NH—CH₂ ImidazolylZ₁: F (2) CF₂ Pyrimidinyl NH—CH₂ Imidazolyl Z₁: F (3) CF₂ PyrimidinylNH—CH₂ Imidazolyl Z₁: F (2) Z₂: F (3) CF₂ Pyrimidinyl NH—CH₂ ImidazolylZ₁: Cl (2) CF₂ Pyrimidinyl NH—CH₂ Imidazolyl Z₁: Cl (3) CF₂ PyrimidinylNH—CH₂ Imidazolyl Z₁: Cl (2) Z₂: Cl (3) CF₂ Pyrimidinyl NH—CH₂Imidazolyl Z₁: F (2) Z₂: Cl (3) CF₂ Pyrimidinyl NH—CH₂ Imidazolyl Z₁: Cl(2) Z₂: F (3) CF₂ Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CH₃ (2) CF₂Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CH₃ (3) CF₂ Pyrimidinyl NH—CH₂Imidazolyl Z₁: CH₂—CH₃ (2) CF₂ Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₃(3) CF₂ Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CF₂ PyrimidinylNH—CH₂ Imidazolyl Z₁: CH₂F (2) CF₂ Pyrimidinyl NH—CH₂ Imidazolyl Z₁:CH₂F (3) CF₂ Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CHF₂ (2) CF₂ PyrimidinylNH—CH₂ Imidazolyl Z₁: CHF₂ (3) CF₂ Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CF₃(2) CF₂ Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CF₃ (3) CF₂ Pyrimidinyl NH—CH₂Imidazolyl Z₁: CH₂—CH₂F (2) CF₂ Pyrimidinyl NH—CH₂ Imidazolyl Z₁:CH₂—CH₂F (3) CF₂ Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CH₂—CHF₂ (2) CF₂Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CH₂—CHF₂ (3) CF₂ Pyrimidinyl NH—CH₂Imidazolyl Z₁: CH₂—CF₃ (2) CF₂ Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CH₂—CF₃(3) CF₂ Pyrimidinyl NH—CH₂ Furanyl None CF₂ Pyrimidinyl NH—CH₂ FuranylZ₁: F (2) CF₂ Pyrimidinyl NH—CH₂ Furanyl Z₁: F (3) CF₂ PyrimidinylNH—CH₂ Furanyl Z₁: F (2) Z₂: F (3) CF₂ Pyrimidinyl NH—CH₂ Furanyl Z₁: Cl(2) CF₂ Pyrimidinyl NH—CH₂ Furanyl Z₁: Cl (3) CF₂ Pyrimidinyl NH—CH₂Furanyl Z₁: Cl (2) Z₂: Cl (3) CF₂ Pyrimidinyl NH—CH₂ Furanyl Z₁: F (2)Z₂: Cl (3) CF₂ Pyrimidinyl NH—CH₂ Furanyl Z₁: Cl (2) Z₂: F (3) CF₂Pyrimidinyl NH—CH₂ Furanyl Z₁: CH₃ (2) CF₂ Pyrimidinyl NH—CH₂ FuranylZ₁: CH₃ (3) CF₂ Pyrimidinyl NH—CH₂ Furanyl Z₁: CH₂—CH₃ (2) CF₂Pyrimidinyl NH—CH₂ Furanyl Z₁: CH₂—CH₃ (3) CF₂ Pyrimidinyl NH—CH₂Furanyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂ Pyrimidinyl NH—CH₂ Furanyl Z₁:CH₂—CH₂—CH₃ or iPr (3) CF₂ Pyrimidinyl NH—CH₂ Furanyl Z₁: CH₂F (2) CF₂Pyrimidinyl NH—CH₂ Furanyl Z₁: CH₂F (3) CF₂ Pyrimidinyl NH—CH₂ FuranylZ₁: CHF₂ (2) CF₂ Pyrimidinyl NH—CH₂ Furanyl Z₁: CHF₂ (3) CF₂ PyrimidinylNH—CH₂ Furanyl Z₁: CF₃ (2) CF₂ Pyrimidinyl NH—CH₂ Furanyl Z₁: CF₃ (3)CF₂ Pyrimidinyl NH—CH₂ Furanyl Z₁: CH₂—CH₂F (2) CF₂ Pyrimidinyl NH—CH₂Furanyl Z₁: CH₂—CH₂F (3) CF₂ Pyrimidinyl NH—CH₂ Furanyl Z₁: CH₂—CHF₂ (2)CF₂ Pyrimidinyl NH—CH₂ Furanyl Z₁: CH₂—CHF₂ (3) CF₂ Pyrimidinyl NH—CH₂Furanyl Z₁: CH₂—CF₃ (2) CF₂ Pyrimidinyl NH—CH₂ Furanyl Z₁: CH₂—CF₃ (3)CF₂ Pyrimidinyl NH—CH₂ Oxazolyl None CF₂ Pyrimidinyl NH—CH₂ Oxazolyl Z₁:F (2) CF₂ Pyrimidinyl NH—CH₂ Oxazolyl Z₁: F (3) CF₂ Pyrimidinyl NH—CH₂Oxazolyl Z₁: F (2) Z₂: F (3) CF₂ Pyrimidinyl NH—CH₂ Oxazolyl Z₁: Cl (2)CF₂ Pyrimidinyl NH—CH₂ Oxazolyl Z₁: Cl (3) CF₂ Pyrimidinyl NH—CH₂Oxazolyl Z₁: Cl (2) Z₂: Cl (3) CF₂ Pyrimidinyl NH—CH₂ Oxazolyl Z₁: F (2)Z₂: Cl (3) CF₂ Pyrimidinyl NH—CH₂ Oxazolyl Z₁: Cl (2) Z₂: F (3) CF₂Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CH₃ (2) CF₂ Pyrimidinyl NH—CH₂ OxazolylZ₁: CH₃ (3) CF₂ Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₃ (2) CF₂Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₃ (3) CF₂ Pyrimidinyl NH—CH₂Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂ Pyrimidinyl NH—CH₂ Oxazolyl Z₁:CH₂—CH₂—CH₃ or iPr (3) CF₂ Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CH₂F (2) CF₂Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CH₂F (3) CF₂ Pyrimidinyl NH—CH₂ OxazolylZ₁: CHF₂ (2) CF₂ Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CHF₂ (3) CF₂Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CF₃ (2) CF₂ Pyrimidinyl NH—CH₂ OxazolylZ₁: CF₃ (3) CF₂ Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₂F (2) CF₂Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₂F (3) CF₂ Pyrimidinyl NH—CH₂Oxazolyl Z₁: CH₂—CHF₂ (2) CF₂ Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CH₂—CHF₂(3) CF₂ Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CH₂—CF₃ (2) CF₂ PyrimidinylNH—CH₂ Oxazolyl Z₁: CH₂—CF₃ (3) CF₂ Pyrimidinyl NH—CH₂ Thiophenyl NoneCF₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁: F (2) CF₂ Pyrimidinyl NH—CH₂Thiophenyl Z₁: F (3) CF₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁: F (2) Z₂: F(3) CF₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁: Cl (2) CF₂ Pyrimidinyl NH—CH₂Thiophenyl Z₁: Cl (3) CF₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁: Cl (2) Z₂:Cl (3) CF₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁: F (2) Z₂: Cl (3) CF₂Pyrimidinyl NH—CH₂ Thiophenyl Z₁: Cl (2) Z₂: F (3) CF₂ PyrimidinylNH—CH₂ Thiophenyl Z₁: CH₃ (2) CF₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CH₃(3) CF₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₃ (2) CF₂ PyrimidinylNH—CH₂ Thiophenyl Z₁: CH₂—CH₃ (3) CF₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁:CH₂—CH₂—CH₃ or iPr (2) CF₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₂—CH₃or iPr (3) CF₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CH₂F (2) CF₂Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CH₂F (3) CF₂ Pyrimidinyl NH—CH₂Thiophenyl Z₁: CHF₂ (2) CF₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CHF₂ (3)CF₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CF₃ (2) CF₂ Pyrimidinyl NH—CH₂Thiophenyl Z₁: CF₃ (3) CF₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₂F(2) CF₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₂F (3) CF₂ PyrimidinylNH—CH₂ Thiophenyl Z₁: CH₂—CHF₂ (2) CF₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁:CH₂—CHF₂ (3) CF₂ Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CH₂—CF₃ (2) CF₂Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CH₂—CF₃ (3) CF₂ Pyrimidinyl NH—CH₂Thiazolyl None CF₂ Pyrimidinyl NH—CH₂ Thiazolyl Z₁: F (2) CF₂Pyrimidinyl NH—CH₂ Thiazolyl Z₁: F (3) CF₂ Pyrimidinyl NH—CH₂ ThiazolylZ₁: F (2) Z₂: F (3) CF₂ Pyrimidinyl NH—CH₂ Thiazolyl Z₁: Cl (2) CF₂Pyrimidinyl NH—CH₂ Thiazolyl Z₁: Cl (3) CF₂ Pyrimidinyl NH—CH₂ ThiazolylZ₁: Cl (2) Z₂: Cl (3) CF₂ Pyrimidinyl NH—CH₂ Thiazolyl Z₁: F (2) Z₂: Cl(3) CF₂ Pyrimidinyl NH—CH₂ Thiazolyl Z₁: Cl (2) Z₂: F (3) CF₂Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CH₃ (2) CF₂ Pyrimidinyl NH—CH₂Thiazolyl Z₁: CH₃ (3) CF₂ Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₃ (2)CF₂ Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₃ (3) CF₂ Pyrimidinyl NH—CH₂Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂ Pyrimidinyl NH—CH₂ ThiazolylZ₁: CH₂—CH₂—CH₃ or iPr (3) CF₂ Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CH₂F (2)CF₂ Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CH₂F (3) CF₂ Pyrimidinyl NH—CH₂Thiazolyl Z₁: CHF₂ (2) CF₂ Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CHF₂ (3) CF₂Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CF₃ (2) CF₂ Pyrimidinyl NH—CH₂Thiazolyl Z₁: CF₃ (3) CF₂ Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₂F (2)CF₂ Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₂F (3) CF₂ Pyrimidinyl NH—CH₂Thiazolyl Z₁: CH₂—CHF₂ (2) CF₂ Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CH₂—CHF₂(3) CF₂ Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CH₂—CF₃ (2) CF₂ PyrimidinylNH—CH₂ Thiazolyl Z₁: CH₂—CF₃ (3) CF₂ Pyrimidinyl NH—C(O) Phenyl None CF₂Pyrimidinyl NH—C(O) Phenyl Z₁: F (para) CF₂ Pyrimidinyl NH—C(O) phenylZ₁: F (meta) CF₂ Pyrimidinyl NH—C(O) phenyl Z₁: F (ortho) CF₂Pyrimidinyl NH—C(O) phenyl Z₁: F (para) Z₂: F (meta) CF₂ PyrimidinylNH—C(O) Phenyl Z₁: Cl (meta) CF₂ Pyrimidinyl NH—C(O) Phenyl Z₁: Cl(para) CF₂ Pyrimidinyl NH—C(O) Phenyl Z₁: Cl (para) Z₂: Cl (meta) CF₂Pyrimidinyl NH—C(O) Phenyl Z₁: F (para) Z₂: Cl (meta) CF₂ PyrimidinylNH—C(O) Phenyl Z₁: Cl (para) Z₂: F (meta) CF₂ Pyrimidinyl NH—C(O) PhenylZ₁: CH₃ (para) CF₂ Pyrimidinyl NH—C(O) Phenyl Z₁: CH₃ (meta) CF₂Pyrimidinyl NH—C(O) Phenyl Z₁: CH₃ (ortho) CF₂ Pyrimidinyl NH—C(O)Phenyl Z₁: CH₂—CH₃ (para) CF₂ Pyrimidinyl NH—C(O) Phenyl Z₁: CH₂—CH₃(meta) CF₂ Pyrimidinyl NH—C(O) Phenyl Z₁: CH₂—CH₃ (ortho) CF₂Pyrimidinyl NH—C(O) Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CF₂ PyrimidinylNH—C(O) Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CF₂ Pyrimidinyl NH—C(O)Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyrimidinyl NH—C(O) Phenyl Z₁:CH₂F (para) CF₂ Pyrimidinyl NH—C(O) Phenyl Z₁: CH₂F (meta) CF₂Pyrimidinyl NH—C(O) Phenyl Z₁: CH₂F (ortho) CF₂ Pyrimidinyl NH—C(O)Phenyl Z₁: CHF₂ (para) CF₂ Pyrimidinyl NH—C(O) Phenyl Z₁: CHF₂ (meta)CF₂ Pyrimidinyl NH—C(O) Phenyl Z₁: CHF₂ (ortho) CF₂ Pyrimidinyl NH—C(O)Phenyl Z₁: CF₃ (para) CF₂ Pyrimidinyl NH—C(O) Phenyl Z₁: CF₃ (meta) CF₂Pyrimidinyl NH—C(O) Phenyl Z₁: CF₃ (ortho) CF₂ Pyrimidinyl NH—C(O)Phenyl Z₁: CH₂—CH₂F (para) CF₂ Pyrimidinyl NH—C(O) Phenyl Z₁: CH₂—CH₂F(meta) CF₂ Pyrimidinyl NH—C(O) Phenyl Z₁: CH₂—CH₂F (ortho) CF₂Pyrimidinyl NH—C(O) Phenyl Z₁: CH₂—CHF₂ (para) CF₂ Pyrimidinyl NH—C(O)Phenyl Z₁: CH₂—CHF₂ (meta) CF₂ Pyrimidinyl NH—C(O) Phenyl Z₁: CH₂—CHF₂(ortho) CF₂ Pyrimidinyl NH—C(O) Phenyl Z₁: CH₂—CF₃ (para) CF₂Pyrimidinyl NH—C(O) Phenyl Z₁: CH₂—CF₃ (meta) CF₂ Pyrimidinyl NH—C(O)Phenyl Z₁: CH₂—CF₃ (ortho) CF₂ Pyrimidinyl NH—C(O) Pyridinyl None CF₂Pyrimidinyl NH—C(O) Pyridinyl Z₁: F (para) CF₂ Pyrimidinyl NH—C(O)Pyridinyl Z₁: F (meta) CF₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: F (ortho)CF₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: F (para) Z₂: F (meta) CF₂Pyrimidinyl NH—C(O) Pyridinyl Z₁: Cl (meta) CF₂ Pyrimidinyl NH—C(O)Pyridinyl Z₁: Cl (para) CF₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: Cl (para)Z₁: Cl (meta) CF₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: F (para) Z₂: Cl(meta) CF₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: Cl (para) Z₂: F (meta) CF₂Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₃ (para) CF₂ Pyrimidinyl NH—C(O)Pyridinyl Z₁: CH₃ (meta) CF₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₃(ortho) CF₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₃ (para) CF₂Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₃ (meta) CF₂ Pyrimidinyl NH—C(O)Pyridinyl Z₁: CH₂—CH₃ (ortho) CF₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁:CH₂—CH₂—CH₃ or iPr (para) CF₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) CF₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂F(para) CF₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂F (meta) CF₂ PyrimidinylNH—C(O) Pyridinyl Z₁: CH₂F (ortho) CF₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁:CHF₂ (para) CF₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: CHF₂ (meta) CF₂Pyrimidinyl NH—C(O) Pyridinyl Z₁: CHF₂ (ortho) CF₂ Pyrimidinyl NH—C(O)Pyridinyl Z₁: CF₃ (para) CF₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: CF₃(meta) CF₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: CF₃ (ortho) CF₂ PyrimidinylNH—C(O) Pyridinyl Z₁: CH₂—CH₂F (para) CF₂ Pyrimidinyl NH—C(O) PyridinylZ₁: CH₂—CH₂F (meta) CF₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₂F(ortho) CF₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂—CHF₂ (para) CF₂Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂—CHF₂ (meta) CF₂ PyrimidinylNH—C(O) Pyridinyl Z₁: CH₂—CHF₂ (ortho) CF₂ Pyrimidinyl NH—C(O) PyridinylZ₁: CH₂—CF₃ (para) CF₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂—CF₃ (meta)CF₂ Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂—CF₃ (ortho) CF₂ PyrimidinylNH—C(O) Pyrimidinyl None CF₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: F(para) CF₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: F (meta) CF₂ PyrimidinylNH—C(O) Pyrimidinyl Z₁: F (ortho) CF₂ Pyrimidinyl NH—C(O) PyrimidinylZ₁: F (para) Z₂: F (meta) CF₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: Cl(meta) CF₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: Cl (para) CF₂ PyrimidinylNH—C(O) Pyrimidinyl Z₁: Cl (para) Z₂: Cl (meta) CF₂ Pyrimidinyl NH—C(O)Pyrimidinyl Z₁: F (para) Z₂: Cl (meta) CF₂ Pyrimidinyl NH—C(O)Pyrimidinyl Z₁: Cl (para) Z₂: F (meta) CF₂ Pyrimidinyl NH—C(O)Pyrimidinyl Z₁: CH₃ (para) CF₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₃(meta) CF₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₃ (ortho) CF₂Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CH₃ (para) CF₂ PyrimidinylNH—C(O) Pyrimidinyl Z₁: CH₂—CH₃ (meta) CF₂ Pyrimidinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CH₃ (ortho) CF₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (para) CF₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) CF₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₂F(para) CF₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₂F (meta) CF₂Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₂F (ortho) CF₂ Pyrimidinyl NH—C(O)Pyrimidinyl Z₁: CHF₂ (para) CF₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CHF₂(meta) CF₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CHF₂ (ortho) CF₂Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CF₃ (para) CF₂ Pyrimidinyl NH—C(O)Pyrimidinyl Z₁: CF₃ (meta) CF₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CF₃(ortho) CF₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CH₂F (para) CF₂Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CH₂F (meta) CF₂ PyrimidinylNH—C(O) Pyrimidinyl Z₁: CH₂—CH₂F (ortho) CF₂ Pyrimidinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CHF₂ (para) CF₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CHF₂ (meta) CF₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CHF₂ (ortho)CF₂ Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CF₃ (para) CF₂ PyrimidinylNH—C(O) Pyrimidinyl Z₁: CH₂—CF₃ (meta) CF₂ Pyrimidinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CF₃ (ortho) CF₂ Pyrimidinyl NH—C(O) Pyrazinyl NoneCF₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: F (para) CF₂ Pyrimidinyl NH—C(O)Pyrazinyl Z₁: F (meta) CF₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: F (ortho)CF₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: F (para) Z₂: F (meta) CF₂Pyrimidinyl NH—C(O) Pyrazinyl Z₁: Cl (meta) CF₂ Pyrimidinyl NH—C(O)Pyrazinyl Z₁: Cl (para) CF₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: Cl (para)Z₂: Cl (meta) CF₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: F (para) Z₂: Cl(meta) CF₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: Cl (para) Z₂: F (meta) CF₂Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₃ (para) CF₂ Pyrimidinyl NH—C(O)Pyrazinyl Z₁: CH₃ (meta) CF₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₃(ortho) CF₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₂—CH₃ (para) CF₂Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₂—CH₃ (meta) CF₂ Pyrimidinyl NH—C(O)Pyrazinyl Z₁: CH₂—CH₃ (ortho) CF₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (para) CF₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) CF₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₂F(para) CF₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₂F (meta) CF₂ PyrimidinylNH—C(O) Pyrazinyl Z₁: CH₂F (ortho) CF₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁:CHF₂ (para) CF₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CHF₂ (meta) CF₂Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CHF₂ (ortho) CF₂ Pyrimidinyl NH—C(O)Pyrazinyl Z₁: CF₃ (para) CF₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CF₃(meta) CF₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CF₃ (ortho) CF₂ PyrimidinylNH—C(O) Pyrazinyl Z₁: CH₂—CH₂F (para) CF₂ Pyrimidinyl NH—C(O) PyrazinylZ₁: CH₂—CH₂F (meta) CF₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₂—CH₂F(ortho) CF₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₂—CHF₂ (para) CF₂Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₂—CHF₂ (meta) CF₂ PyrimidinylNH—C(O) Pyrazinyl Z₁: CH₂—CHF₂ (ortho) CF₂ Pyrimidinyl NH—C(O) PyrazinylZ₁: CH₂—CF₃ (para) CF₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₂—CF₃ (meta)CF₂ Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₂—CF₃ (ortho) CF₂ PyrimidinylNH—C(O) Pyrrolyl None CF₂ Pyrimidinyl NH—C(O) Pyrrolyl Z₁: F (2) CF₂Pyrimidinyl NH—C(O) Pyrrolyl Z₁: F (3) CF₂ Pyrimidinyl NH—C(O) PyrrolylZ₁: F (2) Z₂: F (3) CF₂ Pyrimidinyl NH—C(O) Pyrrolyl Z₁: Cl (2) CF₂Pyrimidinyl NH—C(O) Pyrrolyl Z₁: Cl (3) CF₂ Pyrimidinyl NH—C(O) PyrrolylZ₁: Cl (2) Z₂: Cl (3) CF₂ Pyrimidinyl NH—C(O) Pyrrolyl Z₁: F (2) Z₂: Cl(3) CF₂ Pyrimidinyl NH—C(O) Pyrrolyl Z₁: Cl (2) Z₂: F (3) CF₂Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CH₃ (2) CF₂ Pyrimidinyl NH—C(O)Pyrrolyl Z₁: CH₃ (3) CF₂ Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₃ (2)CF₂ Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₃ (3) CF₂ Pyrimidinyl NH—C(O)Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂ Pyrimidinyl NH—C(O) Pyrrolyl Z₁:CH₂—CH₂—CH₃ or iPr (3) CF₂ Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CH₂F (2) CF₂Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CH₂F (3) CF₂ Pyrimidinyl NH—C(O)Pyrrolyl Z₁: CHF₂ (2) CF₂ Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CHF₂ (3) CF₂Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CF₃ (2) CF₂ Pyrimidinyl NH—C(O)Pyrrolyl Z₁: CF₃ (3) CF₂ Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₂F (2)CF₂ Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₂F (3) CF₂ PyrimidinylNH—C(O) Pyrrolyl Z₁: CH₂—CHF₂ (2) CF₂ Pyrimidinyl NH—C(O) Pyrrolyl Z₁:CH₂—CHF₂ (3) CF₂ Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CH₂—CF₃ (2) CF₂Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CH₂—CF₃ (3) CF₂ Pyrimidinyl NH—C(O)Imidazolyl None CF₂ Pyrimidinyl NH—C(O) Imidazolyl Z₁: F (2) CF₂Pyrimidinyl NH—C(O) Imidazolyl Z₁: F (3) CF₂ Pyrimidinyl NH—C(O)Imidazolyl Z₁: F (2) Z₂: F (3) CF₂ Pyrimidinyl NH—C(O) Imidazolyl Z₁: Cl(2) CF₂ Pyrimidinyl NH—C(O) Imidazolyl Z₁: Cl (3) CF₂ PyrimidinylNH—C(O) Imidazolyl Z₁: Cl (2) Z₂: Cl (3) CF₂ Pyrimidinyl NH—C(O)Imidazolyl Z₁: F (2) Z₂: Cl (3) CF₂ Pyrimidinyl NH—C(O) Imidazolyl Z₁:Cl (2) Z₂: F (3) CF₂ Pyrimidinyl NH—C(O) Imidazolyl Z₁: CH₃ (2) CF₂Pyrimidinyl NH—C(O) Imidazolyl Z₁: CH₃ (3) CF₂ Pyrimidinyl NH—C(O)Imidazolyl Z₁: CH₂—CH₃ (2) CF₂ Pyrimidinyl NH—C(O) Imidazolyl Z₁:CH₂—CH₃ (3) CF₂ Pyrimidinyl NH—C(O) Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr(2) CF₂ Pyrimidinyl NH—C(O) Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CF₂Pyrimidinyl NH—C(O) Imidazolyl Z₁: CH₂F (2) CF₂ Pyrimidinyl NH—C(O)Imidazolyl Z₁: CH₂F (3) CF₂ Pyrimidinyl NH—C(O) Imidazolyl Z₁: CHF₂ (2)CF₂ Pyrimidinyl NH—C(O) Imidazolyl Z₁: CHF₂ (3) CF₂ Pyrimidinyl NH—C(O)Imidazolyl Z₁: CF₃ (2) CF₂ Pyrimidinyl NH—C(O) Imidazolyl Z₁: CF₃ (3)CF₂ Pyrimidinyl NH—C(O) Imidazolyl Z₁: CH₂—CH₂F (2) CF₂ PyrimidinylNH—C(O) Imidazolyl Z₁: CH₂—CH₂F (3) CF₂ Pyrimidinyl NH—C(O) ImidazolylZ₁: CH₂—CHF₂ (2) CF₂ Pyrimidinyl NH—C(O) Imidazolyl Z₁: CH₂—CHF₂ (3) CF₂Pyrimidinyl NH—C(O) Imidazolyl Z₁: CH₂—CF₃ (2) CF₂ Pyrimidinyl NH—C(O)Imidazolyl Z₁: CH₂—CF₃ (3) CF₂ Pyrimidinyl NH—C(O) Furanyl None CF₂Pyrimidinyl NH—C(O) Furanyl Z₁: F (2) CF₂ Pyrimidinyl NH—C(O) FuranylZ₁: F (3) CF₂ Pyrimidinyl NH—C(O) Furanyl Z₁: F (2) Z₂: F (3) CF₂Pyrimidinyl NH—C(O) Furanyl Z₁: Cl (2) CF₂ Pyrimidinyl NH—C(O) FuranylZ₁: Cl (3) CF₂ Pyrimidinyl NH—C(O) Furanyl Z₁: Cl (2) Z₂: Cl (3) CF₂Pyrimidinyl NH—C(O) Furanyl Z₁: F (2) Z₂: Cl (3) CF₂ Pyrimidinyl NH—C(O)Furanyl Z₁: Cl (2) Z₂: F (3) CF₂ Pyrimidinyl NH—C(O) Furanyl Z₁: CH₃ (2)CF₂ Pyrimidinyl NH—C(O) Furanyl Z₁: CH₃ (3) CF₂ Pyrimidinyl NH—C(O)Furanyl Z₁: CH₂—CH₃ (2) CF₂ Pyrimidinyl NH—C(O) Furanyl Z₁: CH₂—CH₃ (3)CF₂ Pyrimidinyl NH—C(O) Furanyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂Pyrimidinyl NH—C(O) Furanyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CF₂ PyrimidinylNH—C(O) Furanyl Z₁: CH₂F (2) CF₂ Pyrimidinyl NH—C(O) Furanyl Z₁: CH₂F(3) CF₂ Pyrimidinyl NH—C(O) Furanyl Z₁: CHF₂ (2) CF₂ Pyrimidinyl NH—C(O)Furanyl Z₁: CHF₂ (3) CF₂ Pyrimidinyl NH—C(O) Furanyl Z₁: CF₃ (2) CF₂Pyrimidinyl NH—C(O) Furanyl Z₁: CF₃ (3) CF₂ Pyrimidinyl NH—C(O) FuranylZ₁: CH₂—CH₂F (2) CF₂ Pyrimidinyl NH—C(O) Furanyl Z₁: CH₂—CH₂F (3) CF₂Pyrimidinyl NH—C(O) Furanyl Z₁: CH₂—CHF₂ (2) CF₂ Pyrimidinyl NH—C(O)Furanyl Z₁: CH₂—CHF₂ (3) CF₂ Pyrimidinyl NH—C(O) Furanyl Z₁: CH₂—CF₃ (2)CF₂ Pyrimidinyl NH—C(O) Furanyl Z₁: CH₂—CF₃ (3) CF₂ Pyrimidinyl NH—C(O)Oxazolyl None CF₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁: F (2) CF₂ PyrimidinylNH—C(O) Oxazolyl Z₁: F (3) CF₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁: F (2)Z₂: F (3) CF₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁: Cl (2) CF₂ PyrimidinylNH—C(O) Oxazolyl Z₁: Cl (3) CF₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁: Cl (2)Z₂: Cl (3) CF₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁: F (2) Z₂: Cl (3) CF₂Pyrimidinyl NH—C(O) Oxazolyl Z₁: Cl (2) Z₂: F (3) CF₂ PyrimidinylNH—C(O) Oxazolyl Z₁: CH₃ (2) CF₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁: CH₃(3) CF₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₃ (2) CF₂ PyrimidinylNH—C(O) Oxazolyl Z₁: CH₂—CH₃ (3) CF₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁:CH₂—CH₂—CH₃ or iPr (2) CF₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₂—CH₃or iPr (3) CF₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁: CH₂F (2) CF₂ PyrimidinylNH—C(O) Oxazolyl Z₁: CH₂F (3) CF₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁: CHF₂(2) CF₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁: CHF₂ (3) CF₂ PyrimidinylNH—C(O) Oxazolyl Z₁: CF₃ (2) CF₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁: CF₃(3) CF₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₂F (2) CF₂ PyrimidinylNH—C(O) Oxazolyl Z₁: CH₂—CH₂F (3) CF₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁:CH₂—CHF₂ (2) CF₂ Pyrimidinyl NH—C(O) Oxazolyl Z₁: CH₂—CHF₂ (3) CF₂Pyrimidinyl NH—C(O) Oxazolyl Z₁: CH₂—CF₃ (2) CF₂ Pyrimidinyl NH—C(O)Oxazolyl Z₁: CH₂—CF₃ (3) CF₂ Pyrimidinyl NH—C(O) Thiophenyl None CF₂Pyrimidinyl NH—C(O) Thiophenyl Z₁: F (2) CF₂ Pyrimidinyl NH—C(O)Thiophenyl Z₁: F (3) CF₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁: F (2) Z₂: F(3) CF₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁: Cl (2) CF₂ PyrimidinylNH—C(O) Thiophenyl Z₁: Cl (3) CF₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁: Cl(2) Z₂: Cl (3) CF₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁: F (2) Z₂: Cl (3)CF₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁: Cl (2) Z₂: F (3) CF₂ PyrimidinylNH—C(O) Thiophenyl Z₁: CH₃ (2) CF₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁:CH₃ (3) CF₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁: CH₂—CH₃ (2) CF₂Pyrimidinyl NH—C(O) Thiophenyl Z₁: CH₂—CH₃ (3) CF₂ Pyrimidinyl NH—C(O)Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂ Pyrimidinyl NH—C(O) ThiophenylZ₁: CH₂—CH₂—CH₃ or iPr (3) CF₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁: CH₂F(2) CF₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁: CH₂F (3) CF₂ PyrimidinylNH—C(O) Thiophenyl Z₁: CHF₂ (2) CF₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁:CHF₂ (3) CF₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁: CF₃ (2) CF₂ PyrimidinylNH—C(O) Thiophenyl Z₁: CF₃ (3) CF₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁:CH₂—CH₂F (2) CF₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁: CH₂—CH₂F (3) CF₂Pyrimidinyl NH—C(O) Thiophenyl Z₁: CH₂—CHF₂ (2) CF₂ Pyrimidinyl NH—C(O)Thiophenyl Z₁: CH₂—CHF₂ (3) CF₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁:CH₂—CF₃ (2) CF₂ Pyrimidinyl NH—C(O) Thiophenyl Z₁: CH₂—CF₃ (3) CF₂Pyrimidinyl NH—C(O) Thiazolyl None CF₂ Pyrimidinyl NH—C(O) Thiazolyl Z₁:F (2) CF₂ Pyrimidinyl NH—C(O) Thiazolyl Z₁: F (3) CF₂ PyrimidinylNH—C(O) Thiazolyl Z₁: F (2) Z₂: F (3) CF₂ Pyrimidinyl NH—C(O) ThiazolylZ₁: Cl (2) CF₂ Pyrimidinyl NH—C(O) Thiazolyl Z₁: Cl (3) CF₂ PyrimidinylNH—C(O) Thiazolyl Z₁: Cl (2) Z₂: Cl (3) CF₂ Pyrimidinyl NH—C(O)Thiazolyl Z₁: F (2) Z₂: Cl (3) CF₂ Pyrimidinyl NH—C(O) Thiazolyl Z₁: Cl(2) Z₂: F (3) CF₂ Pyrimidinyl NH—C(O) Thiazolyl Z₁: CH₃ (2) CF₂Pyrimidinyl NH—C(O) Thiazolyl Z₁: CH₃ (3) CF₂ Pyrimidinyl NH—C(O)Thiazolyl Z₁: CH₂—CH₃ (2) CF₂ Pyrimidinyl NH—C(O) Thiazolyl Z₁: CH₂—CH₃(3) CF₂ Pyrimidinyl NH—C(O) Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂Pyrimidinyl NH—C(O) Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CF₂ PyrimidinylNH—C(O) Thiazolyl Z₁: CH₂F (2) CF₂ Pyrimidinyl NH—C(O) Thiazolyl Z₁:CH₂F (3) CF₂ Pyrimidinyl NH—C(O) Thiazolyl Z₁: CHF₂ (2) CF₂ PyrimidinylNH—C(O) Thiazolyl Z₁: CHF₂ (3) CF₂ Pyrimidinyl NH—C(O) Thiazolyl Z₁: CF₃(2) CF₂ Pyrimidinyl NH—C(O) Thiazolyl Z₁: CF₃ (3) CF₂ PyrimidinylNH—C(O) Thiazolyl Z₁: CH₂—CH₂F (2) CF₂ Pyrimidinyl NH—C(O) Thiazolyl Z₁:CH₂—CH₂F (3) CF₂ Pyrimidinyl NH—C(O) Thiazolyl Z₁: CH₂—CHF₂ (2) CF₂Pyrimidinyl NH—C(O) Thiazolyl Z₁: CH₂—CHF₂ (3) CF₂ Pyrimidinyl NH—C(O)Thiazolyl Z₁: CH₂—CF₃ (2) CF₂ Pyrimidinyl NH—C(O) Thiazolyl Z₁: CH₂—CF₃(3) CF₂ Pyrimidinyl NH—SO₂ Phenyl None CF₂ Pyrimidinyl NH—SO₂ Phenyl Z₁:F (para) CF₂ Pyrimidinyl NH—SO₂ phenyl Z₁: F (meta) CF₂ PyrimidinylNH—SO₂ phenyl Z₁: F (ortho) CF₂ Pyrimidinyl NH—SO₂ phenyl Z₁: F (para)Z₂: F (meta) CF₂ Pyrimidinyl NH—SO₂ Phenyl Z₁: Cl (meta) CF₂ PyrimidinylNH—SO₂ Phenyl Z₁: Cl (para) CF₂ Pyrimidinyl NH—SO₂ Phenyl Z₁: Cl (para)Z₂: Cl (meta) CF₂ Pyrimidinyl NH—SO₂ Phenyl Z₁: F (para) Z₂: Cl (meta)CF₂ Pyrimidinyl NH—SO₂ Phenyl Z₁: Cl (para) Z₂: F (meta) CF₂ PyrimidinylNH—SO₂ Phenyl Z₁: CH₃ (para) CF₂ Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₃(meta) CF₂ Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₃ (ortho) CF₂ PyrimidinylNH—SO₂ Phenyl Z₁: CH₂—CH₃ (para) CF₂ Pyrimidinyl NH—SO₂ Phenyl Z₁:CH₂—CH₃ (meta) CF₂ Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₂—CH₃ (ortho) CF₂Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CF₂ PyrimidinylNH—SO₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CF₂ Pyrimidinyl NH—SO₂Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyrimidinyl NH—SO₂ Phenyl Z₁:CH₂F (para) CF₂ Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₂F (meta) CF₂Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₂F (ortho) CF₂ Pyrimidinyl NH—SO₂ PhenylZ₁: CHF₂ (para) CF₂ Pyrimidinyl NH—SO₂ Phenyl Z₁: CHF₂ (meta) CF₂Pyrimidinyl NH—SO₂ Phenyl Z₁: CHF₂ (ortho) CF₂ Pyrimidinyl NH—SO₂ PhenylZ₁: CF₃ (para) CF₂ Pyrimidinyl NH—SO₂ Phenyl Z₁: CF₃ (meta) CF₂Pyrimidinyl NH—SO₂ Phenyl Z₁: CF₃ (ortho) CF₂ Pyrimidinyl NH—SO₂ PhenylZ₁: CH₂—CH₂F (para) CF₂ Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂F (meta)CF₂ Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂F (ortho) CF₂ PyrimidinylNH—SO₂ Phenyl Z₁: CH₂—CHF₂ (para) CF₂ Pyrimidinyl NH—SO₂ Phenyl Z₁:CH₂—CHF₂ (meta) CF₂ Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₂—CHF₂ (ortho) CF₂Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₂—CF₃ (para) CF₂ Pyrimidinyl NH—SO₂Phenyl Z₁: CH₂—CF₃ (meta) CF₂ Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₂—CF₃(ortho) CF₂ Pyrimidinyl NH—SO₂ Pyridinyl None CF₂ Pyrimidinyl NH—SO₂Pyridinyl Z₁: F (para) CF₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁: F (meta) CF₂Pyrimidinyl NH—SO₂ Pyridinyl Z₁: F (ortho) CF₂ Pyrimidinyl NH—SO₂Pyridinyl Z₁: F (para) Z₂: F (meta) CF₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁:Cl (meta) CF₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁: Cl (para) CF₂ PyrimidinylNH—SO₂ Pyridinyl Z₁: Cl (para) Z₂: Cl (meta) CF₂ Pyrimidinyl NH—SO₂Pyridinyl Z₁: F (para) Z₂: Cl (meta) CF₂ Pyrimidinyl NH—SO₂ PyridinylZ₁: Cl (para) Z₂: F (meta) CF₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₃(para) CF₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₃ (meta) CF₂ PyrimidinylNH—SO₂ Pyridinyl Z₁: CH₃ (ortho) CF₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁:CH₂—CH₃ (para) CF₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₃ (meta) CF₂Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₃ (ortho) CF₂ Pyrimidinyl NH—SO₂Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CF₂ Pyrimidinyl NH—SO₂ PyridinylZ₁: CH₂—CH₂—CH₃ or iPr (meta) CF₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₂F(para) CF₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₂F (meta) CF₂ PyrimidinylNH—SO₂ Pyridinyl Z₁: CH₂F (ortho) CF₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁:CHF₂ (para) CF₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CHF₂ (meta) CF₂Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CHF₂ (ortho) CF₂ Pyrimidinyl NH—SO₂Pyridinyl Z₁: CF₃ (para) CF₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CF₃ (meta)CF₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CF₃ (ortho) CF₂ Pyrimidinyl NH—SO₂Pyridinyl Z₁: CH₂—CH₂F (para) CF₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁:CH₂—CH₂F (meta) CF₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₂F (ortho)CF₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₂—CHF₂ (para) CF₂ PyrimidinylNH—SO₂ Pyridinyl Z₁: CH₂—CHF₂ (meta) CF₂ Pyrimidinyl NH—SO₂ PyridinylZ₁: CH₂—CHF₂ (ortho) CF₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₂—CF₃ (para)CF₂ Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₂—CF₃ (meta) CF₂ PyrimidinylNH—SO₂ Pyridinyl Z₁: CH₂—CF₃ (ortho) CF₂ Pyrimidinyl NH—SO₂ PyrimidinylNone CF₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: F (para) CF₂ PyrimidinylNH—SO₂ Pyrimidinyl Z₁: F (meta) CF₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: F(ortho) CF₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: F (para) Z₂: F (meta) CF₂Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: Cl (meta) CF₂ Pyrimidinyl NH—SO₂Pyrimidinyl Z₁: Cl (para) CF₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: Cl(para) Z₂: Cl (meta) CF₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: F (para) Z₂:Cl (meta) CF₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: Cl (para) Z₂: F (meta)CF₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₃ (para) CF₂ Pyrimidinyl NH—SO₂Pyrimidinyl Z₁: CH₃ (meta) CF₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₃(ortho) CF₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₃ (para) CF₂Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₃ (meta) CF₂ Pyrimidinyl NH—SO₂Pyrimidinyl Z₁: CH₂—CH₃ (ortho) CF₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (para) CF₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) CF₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₂F(para) CF₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₂F (meta) CF₂Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₂F (ortho) CF₂ Pyrimidinyl NH—SO₂Pyrimidinyl Z₁: CHF₂ (para) CF₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CHF₂(meta) CF₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CHF₂ (ortho) CF₂Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CF₃ (para) CF₂ Pyrimidinyl NH—SO₂Pyrimidinyl Z₁: CF₃ (meta) CF₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CF₃(ortho) CF₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂F (para) CF₂Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂F (meta) CF₂ PyrimidinylNH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂F (ortho) CF₂ Pyrimidinyl NH—SO₂Pyrimidinyl Z₁: CH₂—CHF₂ (para) CF₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁:CH₂—CHF₂ (meta) CF₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CHF₂ (ortho)CF₂ Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CF₃ (para) CF₂ PyrimidinylNH—SO₂ Pyrimidinyl Z₁: CH₂—CF₃ (meta) CF₂ Pyrimidinyl NH—SO₂ PyrimidinylZ₁: CH₂—CF₃ (ortho) CF₂ Pyrimidinyl NH—SO₂ Pyrazinyl None CF₂Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: F (para) CF₂ Pyrimidinyl NH—SO₂Pyrazinyl Z₁: F (meta) CF₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: F (ortho)CF₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: F (para) Z₂: F (meta) CF₂Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: Cl (meta) CF₂ Pyrimidinyl NH—SO₂Pyrazinyl Z₁: Cl (para) CF₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: Cl (para)Z₂: Cl (meta) CF₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: F (para) Z₂: Cl(meta) CF₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: Cl (para) Z₂: F (meta) CF₂Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₃ (para) CF₂ Pyrimidinyl NH—SO₂Pyrazinyl Z₁: CH₃ (meta) CF₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₃(ortho) CF₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₃ (para) CF₂Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₃ (meta) CF₂ Pyrimidinyl NH—SO₂Pyrazinyl Z₁: CH₂—CH₃ (ortho) CF₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (para) CF₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) CF₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₂F(para) CF₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₂F (meta) CF₂ PyrimidinylNH—SO₂ Pyrazinyl Z₁: CH₂F (ortho) CF₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁:CHF₂ (para) CF₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CHF₂ (meta) CF₂Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CHF₂ (ortho) CF₂ Pyrimidinyl NH—SO₂Pyrazinyl Z₁: CF₃ (para) CF₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CF₃ (meta)CF₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CF₃ (ortho) CF₂ Pyrimidinyl NH—SO₂Pyrazinyl Z₁: CH₂—CH₂F (para) CF₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁:CH₂—CH₂F (meta) CF₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₂F (ortho)CF₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CHF₂ (para) CF₂ PyrimidinylNH—SO₂ Pyrazinyl Z₁: CH₂—CHF₂ (meta) CF₂ Pyrimidinyl NH—SO₂ PyrazinylZ₁: CH₂—CHF₂ (ortho) CF₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CF₃ (para)CF₂ Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CF₃ (meta) CF₂ PyrimidinylNH—SO₂ Pyrazinyl Z₁: CH₂—CF₃ (ortho) CF₂ Pyrimidinyl NH—SO₂ PyrrolylNone CF₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: F (2) CF₂ Pyrimidinyl NH—SO₂Pyrrolyl Z₁: F (3) CF₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: F (2) Z₂: F (3)CF₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: Cl (2) CF₂ Pyrimidinyl NH—SO₂Pyrrolyl Z₁: Cl (3) CF₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: Cl (2) Z₂: Cl(3) CF₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: F (2) Z₂: Cl (3) CF₂ PyrimidinylNH—SO₂ Pyrrolyl Z₁: Cl (2) Z₂: F (3) CF₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁:CH₃ (2) CF₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: CH₃ (3) CF₂ PyrimidinylNH—SO₂ Pyrrolyl Z₁: CH₂—CH₃ (2) CF₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁:CH₂—CH₃ (3) CF₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (2)CF₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CF₂Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: CH₂F (2) CF₂ Pyrimidinyl NH—SO₂ PyrrolylZ₁: CH₂F (3) CF₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: CHF₂ (2) CF₂Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: CHF₂ (3) CF₂ Pyrimidinyl NH—SO₂ PyrrolylZ₁: CF₃ (2) CF₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: CF₃ (3) CF₂ PyrimidinylNH—SO₂ Pyrrolyl Z₁: CH₂—CH₂F (2) CF₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁:CH₂—CH₂F (3) CF₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CHF₂ (2) CF₂Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CHF₂ (3) CF₂ Pyrimidinyl NH—SO₂Pyrrolyl Z₁: CH₂—CF₃ (2) CF₂ Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CF₃ (3)CF₂ Pyrimidinyl NH—SO₂ Imidazolyl None CF₂ Pyrimidinyl NH—SO₂ ImidazolylZ₁: F (2) CF₂ Pyrimidinyl NH—SO₂ Imidazolyl Z₁: F (3) CF₂ PyrimidinylNH—SO₂ Imidazolyl Z₁: F (2) Z₂: F (3) CF₂ Pyrimidinyl NH—SO₂ ImidazolylZ₁: Cl (2) CF₂ Pyrimidinyl NH—SO₂ Imidazolyl Z₁: Cl (3) CF₂ PyrimidinylNH—SO₂ Imidazolyl Z₁: Cl (2) Z₂: Cl (3) CF₂ Pyrimidinyl NH—SO₂Imidazolyl Z₁: F (2) Z₂: Cl (3) CF₂ Pyrimidinyl NH—SO₂ Imidazolyl Z₁: Cl(2) Z₂: F (3) CF₂ Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CH₃ (2) CF₂Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CH₃ (3) CF₂ Pyrimidinyl NH—SO₂Imidazolyl Z₁: CH₂—CH₃ (2) CF₂ Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₃(3) CF₂ Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CF₂ PyrimidinylNH—SO₂ Imidazolyl Z₁: CH₂F (2) CF₂ Pyrimidinyl NH—SO₂ Imidazolyl Z₁:CH₂F (3) CF₂ Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CHF₂ (2) CF₂ PyrimidinylNH—SO₂ Imidazolyl Z₁: CHF₂ (3) CF₂ Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CF₃(2) CF₂ Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CF₃ (3) CF₂ Pyrimidinyl NH—SO₂Imidazolyl Z₁: CH₂—CH₂F (2) CF₂ Pyrimidinyl NH—SO₂ Imidazolyl Z₁:CH₂—CH₂F (3) CF₂ Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CH₂—CHF₂ (2) CF₂Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CH₂—CHF₂ (3) CF₂ Pyrimidinyl NH—SO₂Imidazolyl Z₁: CH₂—CF₃ (2) CF₂ Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CH₂—CF₃(3) CF₂ Pyrimidinyl NH—SO₂ Furanyl None CF₂ Pyrimidinyl NH—SO₂ FuranylZ₁: F (2) CF₂ Pyrimidinyl NH—SO₂ Furanyl Z₁: F (3) CF₂ PyrimidinylNH—SO₂ Furanyl Z₁: F (2) Z₂: F (3) CF₂ Pyrimidinyl NH—SO₂ Furanyl Z₁: Cl(2) CF₂ Pyrimidinyl NH—SO₂ Furanyl Z₁: Cl (3) CF₂ Pyrimidinyl NH—SO₂Furanyl Z₁: Cl (2) Z₂: Cl (3) CF₂ Pyrimidinyl NH—SO₂ Furanyl Z₁: F (2)Z₂: Cl (3) CF₂ Pyrimidinyl NH—SO₂ Furanyl Z₁: Cl (2) Z₂: F (3) CF₂Pyrimidinyl NH—SO₂ Furanyl Z₁: CH₃ (2) CF₂ Pyrimidinyl NH—SO₂ FuranylZ₁: CH₃ (3) CF₂ Pyrimidinyl NH—SO₂ Furanyl Z₁: CH₂—CH₃ (2) CF₂Pyrimidinyl NH—SO₂ Furanyl Z₁: CH₂—CH₃ (3) CF₂ Pyrimidinyl NH—SO₂Furanyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂ Pyrimidinyl NH—SO₂ Furanyl Z₁:CH₂—CH₂—CH₃ or iPr (3) CF₂ Pyrimidinyl NH—SO₂ Furanyl Z₁: CH₂F (2) CF₂Pyrimidinyl NH—SO₂ Furanyl Z₁: CH₂F (3) CF₂ Pyrimidinyl NH—SO₂ FuranylZ₁: CHF₂ (2) CF₂ Pyrimidinyl NH—SO₂ Furanyl Z₁: CHF₂ (3) CF₂ PyrimidinylNH—SO₂ Furanyl Z₁: CF₃ (2) CF₂ Pyrimidinyl NH—SO₂ Furanyl Z₁: CF₃ (3)CF₂ Pyrimidinyl NH—SO₂ Furanyl Z₁: CH₂—CH₂F (2) CF₂ Pyrimidinyl NH—SO₂Furanyl Z₁: CH₂—CH₂F (3) CF₂ Pyrimidinyl NH—SO₂ Furanyl Z₁: CH₂—CHF₂ (2)CF₂ Pyrimidinyl NH—SO₂ Furanyl Z₁: CH₂—CHF₂ (3) CF₂ Pyrimidinyl NH—SO₂Furanyl Z₁: CH₂—CF₃ (2) CF₂ Pyrimidinyl NH—SO₂ Furanyl Z₁: CH₂—CF₃ (3)CF₂ Pyrimidinyl NH—SO₂ Oxazolyl None CF₂ Pyrimidinyl NH—SO₂ Oxazolyl Z₁:F (2) CF₂ Pyrimidinyl NH—SO₂ Oxazolyl Z₁: F (3) CF₂ Pyrimidinyl NH—SO₂Oxazolyl Z₁: F (2) Z₂: F (3) CF₂ Pyrimidinyl NH—SO₂ Oxazolyl Z₁: Cl (2)CF₂ Pyrimidinyl NH—SO₂ Oxazolyl Z₁: Cl (3) CF₂ Pyrimidinyl NH—SO₂Oxazolyl Z₁: Cl (2) Z₂: Cl (3) CF₂ Pyrimidinyl NH—SO₂ Oxazolyl Z₁: F (2)Z₂: Cl (3) CF₂ Pyrimidinyl NH—SO₂ Oxazolyl Z₁: Cl (2) Z₂: F (3) CF₂Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CH₃ (2) CF₂ Pyrimidinyl NH—SO₂ OxazolylZ₁: CH₃ (3) CF₂ Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CH₂—CH₃ (2) CF₂Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CH₂—CH₃ (3) CF₂ Pyrimidinyl NH—SO₂Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂ Pyrimidinyl NH—SO₂ Oxazolyl Z₁:CH₂—CH₂—CH₃ or iPr (3) CF₂ Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CH₂F (2) CF₂Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CH₂F (3) CF₂ Pyrimidinyl NH—SO₂ OxazolylZ₁: CHF₂ (2) CF₂ Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CHF₂ (3) CF₂Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CF₃ (2) CF₂ Pyrimidinyl NH—SO₂ OxazolylZ₁: CF₃ (3) CF₂ Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CH₂—CH₂F (2) CF₂Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CH₂—CH₂F (3) CF₂ Pyrimidinyl NH—SO₂Oxazolyl Z₁: CH₂—CHF₂ (2) CF₂ Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CH₂—CHF₂(3) CF₂ Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CH₂—CF₃ (2) CF₂ PyrimidinylNH—SO₂ Oxazolyl Z₁: CH₂—CF₃ (3) CF₂ Pyrimidinyl NH—SO₂ Thiophenyl NoneCF₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁: F (2) CF₂ Pyrimidinyl NH—SO₂Thiophenyl Z₁: F (3) CF₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁: F (2) Z₂: F(3) CF₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁: Cl (2) CF₂ Pyrimidinyl NH—SO₂Thiophenyl Z₁: Cl (3) CF₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁: Cl (2) Z₂:Cl (3) CF₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁: F (2) Z₂: Cl (3) CF₂Pyrimidinyl NH—SO₂ Thiophenyl Z₁: Cl (2) Z₂: F (3) CF₂ PyrimidinylNH—SO₂ Thiophenyl Z₁: CH₃ (2) CF₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CH₃(3) CF₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₃ (2) CF₂ PyrimidinylNH—SO₂ Thiophenyl Z₁: CH₂—CH₃ (3) CF₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁:CH₂—CH₂—CH₃ or iPr (2) CF₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₂—CH₃or iPr (3) CF₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CH₂F (2) CF₂Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CH₂F (3) CF₂ Pyrimidinyl NH—SO₂Thiophenyl Z₁: CHF₂ (2) CF₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CHF₂ (3)CF₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CF₃ (2) CF₂ Pyrimidinyl NH—SO₂Thiophenyl Z₁: CF₃ (3) CF₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₂F(2) CF₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₂F (3) CF₂ PyrimidinylNH—SO₂ Thiophenyl Z₁: CH₂—CHF₂ (2) CF₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁:CH₂—CHF₂ (3) CF₂ Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CH₂—CF₃ (2) CF₂Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CH₂—CF₃ (3) CF₂ Pyrimidinyl NH—SO₂Thiazolyl None CF₂ Pyrimidinyl NH—SO₂ Thiazolyl Z₁: F (2) CF₂Pyrimidinyl NH—SO₂ Thiazolyl Z₁: F (3) CF₂ Pyrimidinyl NH—SO₂ ThiazolylZ₁: F (2) Z₂: F (3) CF₂ Pyrimidinyl NH—SO₂ Thiazolyl Z₁: Cl (2) CF₂Pyrimidinyl NH—SO₂ Thiazolyl Z₁: Cl (3) CF₂ Pyrimidinyl NH—SO₂ ThiazolylZ₁: Cl (2) Z₂: Cl (3) CF₂ Pyrimidinyl NH—SO₂ Thiazolyl Z₁: F (2) Z₂: Cl(3) CF₂ Pyrimidinyl NH—SO₂ Thiazolyl Z₁: Cl (2) Z₂: F (3) CF₂Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CH₃ (2) CF₂ Pyrimidinyl NH—SO₂Thiazolyl Z₁: CH₃ (3) CF₂ Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₃ (2)CF₂ Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₃ (3) CF₂ Pyrimidinyl NH—SO₂Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂ Pyrimidinyl NH—SO₂ ThiazolylZ₁: CH₂—CH₂—CH₃ or iPr (3) CF₂ Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CH₂F (2)CF₂ Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CH₂F (3) CF₂ Pyrimidinyl NH—SO₂Thiazolyl Z₁: CHF₂ (2) CF₂ Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CHF₂ (3) CF₂Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CF₃ (2) CF₂ Pyrimidinyl NH—SO₂Thiazolyl Z₁: CF₃ (3) CF₂ Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₂F (2)CF₂ Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₂F (3) CF₂ Pyrimidinyl NH—SO₂Thiazolyl Z₁: CH₂—CHF₂ (2) CF₂ Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CH₂—CHF₂(3) CF₂ Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CH₂—CF₃ (2) CF₂ PyrimidinylNH—SO₂ Thiazolyl Z₁: CH₂—CF₃ (3) CF₂ Pyrazinyl NH—CH₂ Phenyl None CF₂Pyrazinyl NH—CH₂ Phenyl Z₁: F (para) CF₂ Pyrazinyl NH—CH₂ phenyl Z₁: F(meta) CF₂ Pyrazinyl NH—CH₂ phenyl Z₁: F (ortho) CF₂ Pyrazinyl NH—CH₂phenyl Z₁: F (para) Z₂: F meta) CF₂ Pyrazinyl NH—CH₂ Phenyl Z₁: Cl(meta) CF₂ Pyrazinyl NH—CH₂ Phenyl Z₁: Cl (para) CF₂ Pyrazinyl NH—CH₂Phenyl Z₁: Cl (para) Z₂: Cl (meta) CF₂ Pyrazinyl NH—CH₂ Phenyl Z₁: F(para) Z₂: Cl (meta) CF₂ Pyrazinyl NH—CH₂ Phenyl Z₁: Cl (para) Z₂: F(meta) CF₂ Pyrazinyl NH—CH₂ Phenyl Z₁: CH₃ (para) CF₂ Pyrazinyl NH—CH₂Phenyl Z₁: CH₃ (meta) CF₂ Pyrazinyl NH—CH₂ Phenyl Z₁: CH₃ (ortho) CF₂Pyrazinyl NH—CH₂ Phenyl Z₁: CH₂—CH₃ (para) CF₂ Pyrazinyl NH—CH₂ PhenylZ₁: CH₂—CH₃ (meta) CF₂ Pyrazinyl NH—CH₂ Phenyl Z₁: CH₂—CH₃ (ortho) CF₂Pyrazinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CF₂ PyrazinylNH—CH₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CF₂ Pyrazinyl NH—CH₂ PhenylZ₁: CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyrazinyl NH—CH₂ Phenyl Z₁: CH₂F(para) CF₂ Pyrazinyl NH—CH₂ Phenyl Z₁: CH₂F (meta) CF₂ Pyrazinyl NH—CH₂Phenyl Z₁: CH₂F (ortho) CF₂ Pyrazinyl NH—CH₂ Phenyl Z₁: CHF₂ (para) CF₂Pyrazinyl NH—CH₂ Phenyl Z₁: CHF₂ (meta) CF₂ Pyrazinyl NH—CH₂ Phenyl Z₁:CHF₂ (ortho) CF₂ Pyrazinyl NH—CH₂ Phenyl Z₁: CF₃ (para) CF₂ PyrazinylNH—CH₂ Phenyl Z₁: CF₃ (meta) CF₂ Pyrazinyl NH—CH₂ Phenyl Z₁: CF₃ (ortho)CF₂ Pyrazinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂F (para) CF₂ Pyrazinyl NH—CH₂Phenyl Z₁: CH₂—CH₂F (meta) CF₂ Pyrazinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂F(ortho) CF₂ Pyrazinyl NH—CH₂ Phenyl Z₁: CH₂—CHF₂ (para) CF₂ PyrazinylNH—CH₂ Phenyl Z₁: CH₂—CHF₂ (meta) CF₂ Pyrazinyl NH—CH₂ Phenyl Z₁:CH₂—CHF₂ (ortho) CF₂ Pyrazinyl NH—CH₂ Phenyl Z₁: CH₂—CF₃ (para) CF₂Pyrazinyl NH—CH₂ Phenyl Z₁: CH₂—CF₃ (meta) CF₂ Pyrazinyl NH—CH₂ PhenylZ₁: CH₂—CF₃ (ortho) CF₂ Pyrazinyl NH—CH₂ Pyridinyl None CF₂ PyrazinylNH—CH₂ Pyridinyl Z₁: F (para) CF₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: F(meta) CF₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: F (ortho) CF₂ Pyrazinyl NH—CH₂Pyridinyl Z₁: F (para) Z₂: F (meta) CF₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁:Cl (meta) CF₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: Cl (para) CF₂ PyrazinylNH—CH₂ Pyridinyl Z₁: Cl (para) Z₂: Cl (meta) CF₂ Pyrazinyl NH—CH₂Pyridinyl Z₁: F (para) Z₂: Cl (meta) CF₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁:Cl (para) Z₂: F (meta) CF₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₃ (para) CF₂Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₃ (meta) CF₂ Pyrazinyl NH—CH₂ PyridinylZ₁: CH₃ (ortho) CF₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₃ (para) CF₂Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₃ (meta) CF₂ Pyrazinyl NH—CH₂Pyridinyl Z₁: CH₂—CH₃ (ortho) CF₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁:CH₂—CH₂—CH₃ or iPr (para) CF₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₂—CH₃or iPr (meta) CF₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr(ortho) CF₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂F (para) CF₂ PyrazinylNH—CH₂ Pyridinyl Z₁: CH₂F (meta) CF₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂F(ortho) CF₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: CHF₂ (para) CF₂ PyrazinylNH—CH₂ Pyridinyl Z₁: CHF₂ (meta) CF₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: CHF₂(ortho) CF₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: CF₃ (para) CF₂ PyrazinylNH—CH₂ Pyridinyl Z₁: CF₃ (meta) CF₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: CF₃(ortho) CF₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₂F (para) CF₂ PyrazinylNH—CH₂ Pyridinyl Z₁: CH₂—CH₂F (meta) CF₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁:CH₂—CH₂F (ortho) CF₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂—CHF₂ (para) CF₂Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂—CHF₂ (meta) CF₂ Pyrazinyl NH—CH₂Pyridinyl Z₁: CH₂—CHF₂ (ortho) CF₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁:CH₂—CF₃ (para) CF₂ Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂—CF₃ (meta) CF₂Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂—CF₃ (ortho) CF₂ Pyrazinyl NH—CH₂Pyrimidinyl None CF₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: F (para) CF₂Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: F (meta) CF₂ Pyrazinyl NH—CH₂Pyrimidinyl Z₁: F (ortho) CF₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: F (para)Z₂: F (meta) CF₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: Cl (meta) CF₂Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: Cl (para) CF₂ Pyrazinyl NH—CH₂Pyrimidinyl Z₁: Cl (para) Z₂: Cl (meta) CF₂ Pyrazinyl NH—CH₂ PyrimidinylZ₁: F (para) Z₂: Cl (meta) CF₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: Cl(para) Z₂: F (meta) CF₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₃ (para) CF₂Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₃ (meta) CF₂ Pyrazinyl NH—CH₂Pyrimidinyl Z₁: CH₃ (ortho) CF₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₃(para) CF₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₃ (meta) CF₂ PyrazinylNH—CH₂ Pyrimidinyl Z₁: CH₂—CH₃ (ortho) CF₂ Pyrazinyl NH—CH₂ PyrimidinylZ₁: CH₂—CH₂—CH₃ or iPr (para) CF₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) CF₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₂F(para) CF₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₂F (meta) CF₂ PyrazinylNH—CH₂ Pyrimidinyl Z₁: CH₂F (ortho) CF₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁:CHF₂ (para) CF₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CHF₂ (meta) CF₂Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CHF₂ (ortho) CF₂ Pyrazinyl NH—CH₂Pyrimidinyl Z₁: CF₃ (para) CF₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CF₃(meta) CF₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CF₃ (ortho) CF₂ PyrazinylNH—CH₂ Pyrimidinyl Z₁: CH₂—CH₂F (para) CF₂ Pyrazinyl NH—CH₂ PyrimidinylZ₁: CH₂—CH₂F (meta) CF₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₂F(ortho) CF₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CHF₂ (para) CF₂Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CHF₂ (meta) CF₂ Pyrazinyl NH—CH₂Pyrimidinyl Z₁: CH₂—CHF₂ (ortho) CF₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁:CH₂—CF₃ (para) CF₂ Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CF₃ (meta) CF₂Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CF₃ (ortho) CF₂ Pyrazinyl NH—CH₂Pyrazinyl None CF₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: F (para) CF₂ PyrazinylNH—CH₂ Pyrazinyl Z₁: F (meta) CF₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: F(ortho) CF₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: F (para) Z₂: F (meta) CF₂Pyrazinyl NH—CH₂ Pyrazinyl Z₁: Cl (meta) CF₂ Pyrazinyl NH—CH₂ PyrazinylZ₁: Cl (para) CF₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: Cl (para) Z₂: Cl (meta)CF₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: F (para) Z₂: Cl (meta) CF₂ PyrazinylNH—CH₂ Pyrazinyl Z₁: Cl (para) Z₂: F (meta) CF₂ Pyrazinyl NH—CH₂Pyrazinyl Z₁: CH₃ (para) CF₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₃ (meta)CF₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₃ (ortho) CF₂ Pyrazinyl NH—CH₂Pyrazinyl Z₁: CH₂—CH₃ (para) CF₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₃(meta) CF₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₃ (ortho) CF₂ PyrazinylNH—CH₂ Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CF₂ Pyrazinyl NH—CH₂Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CF₂ Pyrazinyl NH—CH₂ PyrazinylZ₁: CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂F(para) CF₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂F (meta) CF₂ PyrazinylNH—CH₂ Pyrazinyl Z₁: CH₂F (ortho) CF₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁:CHF₂ (para) CF₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CHF₂ (meta) CF₂ PyrazinylNH—CH₂ Pyrazinyl Z₁: CHF₂ (ortho) CF₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CF₃(para) CF₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CF₃ (meta) CF₂ PyrazinylNH—CH₂ Pyrazinyl Z₁: CF₃ (ortho) CF₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁:CH₂—CH₂F (para) CF₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₂F (meta) CF₂Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₂F (ortho) CF₂ Pyrazinyl NH—CH₂Pyrazinyl Z₁: CH₂—CHF₂ (para) CF₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁:CH₂—CHF₂ (meta) CF₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CHF₂ (ortho) CF₂Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CF₃ (para) CF₂ Pyrazinyl NH—CH₂Pyrazinyl Z₁: CH₂—CF₃ (meta) CF₂ Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CF₃(ortho) CF₂ Pyrazinyl NH—CH₂ Pyrrolyl None CF₂ Pyrazinyl NH—CH₂ PyrrolylZ₁: F (2) CF₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: F (3) CF₂ Pyrazinyl NH—CH₂Pyrrolyl Z₁: F (2) Z₂: F (3) CF₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: Cl (2)CF₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: Cl (3) CF₂ Pyrazinyl NH—CH₂ PyrrolylZ₁: Cl (2) Z₂: Cl (3) CF₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: F (2) Z₂: Cl (3)CF₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: Cl (2) Z₂: F (3) CF₂ Pyrazinyl NH—CH₂Pyrrolyl Z₁: CH₃ (2) CF₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CH₃ (3) CF₂Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₃ (2) CF₂ Pyrazinyl NH—CH₂ PyrrolylZ₁: CH₂—CH₃ (3) CF₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (2)CF₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CF₂ PyrazinylNH—CH₂ Pyrrolyl Z₁: CH₂F (2) CF₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CH₂F (3)CF₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CHF₂ (2) CF₂ Pyrazinyl NH—CH₂ PyrrolylZ₁: CHF₂ (3) CF₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CF₃ (2) CF₂ PyrazinylNH—CH₂ Pyrrolyl Z₁: CF₃ (3) CF₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₂F(2) CF₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₂F (3) CF₂ Pyrazinyl NH—CH₂Pyrrolyl Z₁: CH₂—CHF₂ (2) CF₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CHF₂ (3)CF₂ Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CF₃ (2) CF₂ Pyrazinyl NH—CH₂Pyrrolyl Z₁: CH₂—CF₃ (3) CF₂ Pyrazinyl NH—CH₂ Imidazolyl None CF₂Pyrazinyl NH—CH₂ Imidazolyl Z₁: F (2) CF₂ Pyrazinyl NH—CH₂ ImidazolylZ₁: F (3) CF₂ Pyrazinyl NH—CH₂ Imidazolyl Z₁: F (2) Z₂: F (3) CF₂Pyrazinyl NH—CH₂ Imidazolyl Z₁: Cl (2) CF₂ Pyrazinyl NH—CH₂ ImidazolylZ₁: Cl (3) CF₂ Pyrazinyl NH—CH₂ Imidazolyl Z₁: Cl (2) Z₂: Cl (3) CF₂Pyrazinyl NH—CH₂ Imidazolyl Z₁: F (2) Z₂: Cl (3) CF₂ Pyrazinyl NH—CH₂Imidazolyl Z₁: Cl (2) Z₂: F (3) CF₂ Pyrazinyl NH—CH₂ Imidazolyl Z₁: CH₃(2) CF₂ Pyrazinyl NH—CH₂ Imidazolyl Z₁: CH₃ (3) CF₂ Pyrazinyl NH—CH₂Imidazolyl Z₁: CH₂—CH₃ (2) CF₂ Pyrazinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₃(3) CF₂ Pyrazinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂Pyrazinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CF₂ PyrazinylNH—CH₂ Imidazolyl Z₁: CH₂F (2) CF₂ Pyrazinyl NH—CH₂ Imidazolyl Z₁: CH₂F(3) CF₂ Pyrazinyl NH—CH₂ Imidazolyl Z₁: CHF₂ (2) CF₂ Pyrazinyl NH—CH₂Imidazolyl Z₁: CHF₂ (3) CF₂ Pyrazinyl NH—CH₂ Imidazolyl Z₁: CF₃ (2) CF₂Pyrazinyl NH—CH₂ Imidazolyl Z₁: CF₃ (3) CF₂ Pyrazinyl NH—CH₂ ImidazolylZ₁: CH₂—CH₂F (2) CF₂ Pyrazinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₂F (3) CF₂Pyrazinyl NH—CH₂ Imidazolyl Z₁: CH₂—CHF₂ (2) CF₂ Pyrazinyl NH—CH₂Imidazolyl Z₁: CH₂—CHF₂ (3) CF₂ Pyrazinyl NH—CH₂ Imidazolyl Z₁: CH₂—CF₃(2) CF₂ Pyrazinyl NH—CH₂ Imidazolyl Z₁: CH₂—CF₃ (3) CF₂ Pyrazinyl NH—CH₂Furanyl None CF₂ Pyrazinyl NH—CH₂ Furanyl Z₁: F (2) CF₂ Pyrazinyl NH—CH₂Furanyl Z₁: F (3) CF₂ Pyrazinyl NH—CH₂ Furanyl Z₁: F (2) Z₂: F (3) CF₂Pyrazinyl NH—CH₂ Furanyl Z₁: Cl (2) CF₂ Pyrazinyl NH—CH₂ Furanyl Z₁: Cl(3) CF₂ Pyrazinyl NH—CH₂ Furanyl Z₁: Cl (2) Z₂: Cl (3) CF₂ PyrazinylNH—CH₂ Furanyl Z₁: F (2) Z₂: Cl (3) CF₂ Pyrazinyl NH—CH₂ Furanyl Z₁: Cl(2) Z₂: F (3) CF₂ Pyrazinyl NH—CH₂ Furanyl Z₁: CH₃ (2) CF₂ PyrazinylNH—CH₂ Furanyl Z₁: CH₃ (3) CF₂ Pyrazinyl NH—CH₂ Furanyl Z₁: CH₂—CH₃ (2)CF₂ Pyrazinyl NH—CH₂ Furanyl Z₁: CH₂—CH₃ (3) CF₂ Pyrazinyl NH—CH₂Furanyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂ Pyrazinyl NH—CH₂ Furanyl Z₁:CH₂—CH₂—CH₃ or iPr (3) CF₂ Pyrazinyl NH—CH₂ Furanyl Z₁: CH₂F (2) CF₂Pyrazinyl NH—CH₂ Furanyl Z₁: CH₂F (3) CF₂ Pyrazinyl NH—CH₂ Furanyl Z₁:CHF₂ (2) CF₂ Pyrazinyl NH—CH₂ Furanyl Z₁: CHF₂ (3) CF₂ Pyrazinyl NH—CH₂Furanyl Z₁: CF₃ (2) CF₂ Pyrazinyl NH—CH₂ Furanyl Z₁: CF₃ (3) CF₂Pyrazinyl NH—CH₂ Furanyl Z₁: CH₂—CH₂F (2) CF₂ Pyrazinyl NH—CH₂ FuranylZ₁: CH₂—CH₂F (3) CF₂ Pyrazinyl NH—CH₂ Furanyl Z₁: CH₂—CHF₂ (2) CF₂Pyrazinyl NH—CH₂ Furanyl Z₁: CH₂—CHF₂ (3) CF₂ Pyrazinyl NH—CH₂ FuranylZ₁: CH₂—CF₃ (2) CF₂ Pyrazinyl NH—CH₂ Furanyl Z₁: CH₂—CF₃ (3) CF₂Pyrazinyl NH—CH₂ Oxazolyl None CF₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁: F (2)CF₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁: F (3) CF₂ Pyrazinyl NH—CH₂ OxazolylZ₁: F (2) Z₂: F (3) CF₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁: Cl (2) CF₂Pyrazinyl NH—CH₂ Oxazolyl Z₁: Cl (3) CF₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁:Cl (2) Z₂: Cl (3) CF₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁: F (2) Z₂: Cl (3) CF₂Pyrazinyl NH—CH₂ Oxazolyl Z₁: Cl (2) Z₂: F (3) CF₂ Pyrazinyl NH—CH₂Oxazolyl Z₁: CH₃ (2) CF₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁: CH₃ (3) CF₂Pyrazinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₃ (2) CF₂ Pyrazinyl NH—CH₂ OxazolylZ₁: CH₂—CH₃ (3) CF₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2)CF₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CF₂ PyrazinylNH—CH₂ Oxazolyl Z₁: CH₂F (2) CF₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁: CH₂F (3)CF₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁: CHF₂ (2) CF₂ Pyrazinyl NH—CH₂ OxazolylZ₁: CHF₂ (3) CF₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁: CF₃ (2) CF₂ PyrazinylNH—CH₂ Oxazolyl Z₁: CF₃ (3) CF₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₂F(2) CF₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₂F (3) CF₂ Pyrazinyl NH—CH₂Oxazolyl Z₁: CH₂—CHF₂ (2) CF₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁: CH₂—CHF₂ (3)CF₂ Pyrazinyl NH—CH₂ Oxazolyl Z₁: CH₂—CF₃ (2) CF₂ Pyrazinyl NH—CH₂Oxazolyl Z₁: CH₂—CF₃ (3) CF₂ Pyrazinyl NH—CH₂ Thiophenyl None CF₂Pyrazinyl NH—CH₂ Thiophenyl Z₁: F (2) CF₂ Pyrazinyl NH—CH₂ ThiophenylZ₁: F (3) CF₂ Pyrazinyl NH—CH₂ Thiophenyl Z₁: F (2) Z₂: F (3) CF₂Pyrazinyl NH—CH₂ Thiophenyl Z₁: Cl (2) CF₂ Pyrazinyl NH—CH₂ ThiophenylZ₁: Cl (3) CF₂ Pyrazinyl NH—CH₂ Thiophenyl Z₁: Cl (2) Z₂: Cl (3) CF₂Pyrazinyl NH—CH₂ Thiophenyl Z₁: F (2) Z₂: Cl (3) CF₂ Pyrazinyl NH—CH₂Thiophenyl Z₁: Cl (2) Z₂: F (3) CF₂ Pyrazinyl NH—CH₂ Thiophenyl Z₁: CH₃(2) CF₂ Pyrazinyl NH—CH₂ Thiophenyl Z₁: CH₃ (3) CF₂ Pyrazinyl NH—CH₂Thiophenyl Z₁: CH₂—CH₃ (2) CF₂ Pyrazinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₃(3) CF₂ Pyrazinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂Pyrazinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CF₂ PyrazinylNH—CH₂ Thiophenyl Z₁: CH₂F (2) CF₂ Pyrazinyl NH—CH₂ Thiophenyl Z₁: CH₂F(3) CF₂ Pyrazinyl NH—CH₂ Thiophenyl Z₁: CHF₂ (2) CF₂ Pyrazinyl NH—CH₂Thiophenyl Z₁: CHF₂ (3) CF₂ Pyrazinyl NH—CH₂ Thiophenyl Z₁: CF₃ (2) CF₂Pyrazinyl NH—CH₂ Thiophenyl Z₁: CF₃ (3) CF₂ Pyrazinyl NH—CH₂ ThiophenylZ₁: CH₂—CH₂F (2) CF₂ Pyrazinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₂F (3) CF₂Pyrazinyl NH—CH₂ Thiophenyl Z₁: CH₂—CHF₂ (2) CF₂ Pyrazinyl NH—CH₂Thiophenyl Z₁: CH₂—CHF₂ (3) CF₂ Pyrazinyl NH—CH₂ Thiophenyl Z₁: CH₂—CF₃(2) CF₂ Pyrazinyl NH—CH₂ Thiophenyl Z₁: CH₂—CF₃ (3) CF₂ Pyrazinyl NH—CH₂Thiazolyl None CF₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁: F (2) CF₂ PyrazinylNH—CH₂ Thiazolyl Z₁: F (3) CF₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁: F (2) Z₂:F (3) CF₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁: Cl (2) CF₂ Pyrazinyl NH—CH₂Thiazolyl Z₁: Cl (3) CF₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁: Cl (2) Z₂: Cl(3) CF₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁: F (2) Z₂: Cl (3) CF₂ PyrazinylNH—CH₂ Thiazolyl Z₁: Cl (2) Z₂: F (3) CF₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁:CH₃ (2) CF₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁: CH₃ (3) CF₂ Pyrazinyl NH—CH₂Thiazolyl Z₁: CH₂—CH₃ (2) CF₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₃ (3)CF₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂ PyrazinylNH—CH₂ Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CF₂ Pyrazinyl NH—CH₂Thiazolyl Z₁: CH₂F (2) CF₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁: CH₂F (3) CF₂Pyrazinyl NH—CH₂ Thiazolyl Z₁: CHF₂ (2) CF₂ Pyrazinyl NH—CH₂ ThiazolylZ₁: CHF₂ (3) CF₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁: CF₃ (2) CF₂ PyrazinylNH—CH₂ Thiazolyl Z₁: CF₃ (3) CF₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₂F(2) CF₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₂F (3) CF₂ Pyrazinyl NH—CH₂Thiazolyl Z₁: CH₂—CHF₂ (2) CF₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁: CH₂—CHF₂(3) CF₂ Pyrazinyl NH—CH₂ Thiazolyl Z₁: CH₂—CF₃ (2) CF₂ Pyrazinyl NH—CH₂Thiazolyl Z₁: CH₂—CF₃ (3) CF₂ Pyrazinyl NH—C(O) Phenyl None CF₂Pyrazinyl NH—C(O) Phenyl Z₁: F (para) CF₂ Pyrazinyl NH—C(O) phenyl Z₁: F(meta) CF₂ Pyrazinyl NH—C(O) phenyl Z₁: F (ortho) CF₂ Pyrazinyl NH—C(O)phenyl Z₁: F (para) Z₂: F (meta) CF₂ Pyrazinyl NH—C(O) Phenyl Z₁: Cl(meta) CF₂ Pyrazinyl NH—C(O) Phenyl Z₁: Cl (para) CF₂ Pyrazinyl NH—C(O)Phenyl Z₁: Cl (para) Z₂: Cl (meta) CF₂ Pyrazinyl NH—C(O) Phenyl Z₁: F(para) Z₂: Cl (meta) CF₂ Pyrazinyl NH—C(O) Phenyl Z₁: Cl (para) Z₂: F(meta) CF₂ Pyrazinyl NH—C(O) Phenyl Z₁: CH₃ (para) CF₂ Pyrazinyl NH—C(O)Phenyl Z₁: CH₃ (meta) CF₂ Pyrazinyl NH—C(O) Phenyl Z₁: CH₃ (ortho) CF₂Pyrazinyl NH—C(O) Phenyl Z₁: CH₂—CH₃ (para) CF₂ Pyrazinyl NH—C(O) PhenylZ₁: CH₂—CH₃ (meta) CF₂ Pyrazinyl NH—C(O) Phenyl Z₁: CH₂—CH₃ (ortho) CF₂Pyrazinyl NH—C(O) Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CF₂ PyrazinylNH—C(O) Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CF₂ Pyrazinyl NH—C(O)Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyrazinyl NH—C(O) Phenyl Z₁:CH₂F (para) CF₂ Pyrazinyl NH—C(O) Phenyl Z₁: CH₂F (meta) CF₂ PyrazinylNH—C(O) Phenyl Z₁: CH₂F (ortho) CF₂ Pyrazinyl NH—C(O) Phenyl Z₁: CHF₂(para) CF₂ Pyrazinyl NH—C(O) Phenyl Z₁: CHF₂ (meta) CF₂ PyrazinylNH—C(O) Phenyl Z₁: CHF₂ (ortho) CF₂ Pyrazinyl NH—C(O) Phenyl Z₁: CF₃(para) CF₂ Pyrazinyl NH—C(O) Phenyl Z₁: CF₃ (meta) CF₂ Pyrazinyl NH—C(O)Phenyl Z₁: CF₃ (ortho) CF₂ Pyrazinyl NH—C(O) Phenyl Z₁: CH₂—CH₂F (para)CF₂ Pyrazinyl NH—C(O) Phenyl Z₁: CH₂—CH₂F (meta) CF₂ Pyrazinyl NH—C(O)Phenyl Z₁: CH₂—CH₂F (ortho) CF₂ Pyrazinyl NH—C(O) Phenyl Z₁: CH₂—CHF₂(para) CF₂ Pyrazinyl NH—C(O) Phenyl Z₁: CH₂—CHF₂ (meta) CF₂ PyrazinylNH—C(O) Phenyl Z₁: CH₂—CHF₂ (ortho) CF₂ Pyrazinyl NH—C(O) Phenyl Z₁:CH₂—CF₃ (para) CF₂ Pyrazinyl NH—C(O) Phenyl Z₁: CH₂—CF₃ (meta) CF₂Pyrazinyl NH—C(O) Phenyl Z₁: CH₂—CF₃ (ortho) CF₂ Pyrazinyl NH—C(O)Pyridinyl None CF₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: F (para) CF₂Pyrazinyl NH—C(O) Pyridinyl Z₁: F (meta) CF₂ Pyrazinyl NH—C(O) PyridinylZ₁: F (ortho) CF₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: F (para) Z₂: F (meta)CF₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: Cl (meta) CF₂ Pyrazinyl NH—C(O)Pyridinyl Z₁: Cl (para) CF₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: Cl (para)Z₂: Cl (meta) CF₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: F (para) Z₂: Cl (meta)CF₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: Cl (para) Z₂: F (meta) CF₂ PyrazinylNH—C(O) Pyridinyl Z₁: CH₃ (para) CF₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₃(meta) CF₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₃ (ortho) CF₂ PyrazinylNH—C(O) Pyridinyl Z₁: CH₂—CH₃ (para) CF₂ Pyrazinyl NH—C(O) Pyridinyl Z₁:CH₂—CH₃ (meta) CF₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₃ (ortho) CF₂Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CF₂ PyrazinylNH—C(O) Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CF₂ Pyrazinyl NH—C(O)Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyrazinyl NH—C(O) PyridinylZ₁: CH₂F (para) CF₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₂F (meta) CF₂Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₂F (ortho) CF₂ Pyrazinyl NH—C(O)Pyridinyl Z₁: CHF₂ (para) CF₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: CHF₂(meta) CF₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: CHF₂ (ortho) CF₂ PyrazinylNH—C(O) Pyridinyl Z₁: CF₃ (para) CF₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: CF₃(meta) CF₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: CF₃ (ortho) CF₂ PyrazinylNH—C(O) Pyridinyl Z₁: CH₂—CH₂F (para) CF₂ Pyrazinyl NH—C(O) PyridinylZ₁: CH₂—CH₂F (meta) CF₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₂F (ortho)CF₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₂—CHF₂ (para) CF₂ PyrazinylNH—C(O) Pyridinyl Z₁: CH₂—CHF₂ (meta) CF₂ Pyrazinyl NH—C(O) PyridinylZ₁: CH₂—CHF₂ (ortho) CF₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₂—CF₃ (para)CF₂ Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₂—CF₃ (meta) CF₂ Pyrazinyl NH—C(O)Pyridinyl Z₁: CH₂—CF₃ (ortho) CF₂ Pyrazinyl NH—C(O) Pyrimidinyl None CF₂Pyrazinyl NH—C(O) Pyrimidinyl Z₁: F (para) CF₂ Pyrazinyl NH—C(O)Pyrimidinyl Z₁: F (meta) CF₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: F (ortho)CF₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: F (para) Z₂: F (meta) CF₂Pyrazinyl NH—C(O) Pyrimidinyl Z₁: Cl (meta) CF₂ Pyrazinyl NH—C(O)Pyrimidinyl Z₁: Cl (para) CF₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: Cl(para) Z₂: Cl (meta) CF₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: F (para) Z₂:Cl (meta) CF₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: Cl (para) Z₂: F (meta)CF₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₃ (para) CF₂ Pyrazinyl NH—C(O)Pyrimidinyl Z₁: CH₃ (meta) CF₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₃(ortho) CF₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CH₃ (para) CF₂Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CH₃ (meta) CF₂ Pyrazinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CH₃ (ortho) CF₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (para) CF₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) CF₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₂F(para) CF₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₂F (meta) CF₂ PyrazinylNH—C(O) Pyrimidinyl Z₁: CH₂F (ortho) CF₂ Pyrazinyl NH—C(O) PyrimidinylZ₁: CH₂ (para) CF₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₂ (meta) CF₂Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₂ (ortho) CF₂ Pyrazinyl NH—C(O)Pyrimidinyl Z₁: CF₃ (para) CF₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CF₃(meta) CF₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CF₃ (ortho) CF₂ PyrazinylNH—C(O) Pyrimidinyl Z₁: CH₂—CH₂F (para) CF₂ Pyrazinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CH₂F (meta) CF₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CH₂F (ortho) CF₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CHF₂ (para)CF₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CHF₂ (meta) CF₂ PyrazinylNH—C(O) Pyrimidinyl Z₁: CH₂—CHF₂ (ortho) CF₂ Pyrazinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CF₃ (para) CF₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CF₃ (meta) CF₂ Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CF₃ (ortho) CF₂Pyrazinyl NH—C(O) Pyrazinyl None CF₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: F(para) CF₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: F (meta) CF₂ PyrazinylNH—C(O) Pyrazinyl Z₁: F (ortho) CF₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: F(para) Z₂: F (meta) CF₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: Cl (meta) CF₂Pyrazinyl NH—C(O) Pyrazinyl Z₁: Cl (para) CF₂ Pyrazinyl NH—C(O)Pyrazinyl Z₁: Cl (para) Z₂: Cl (meta) CF₂ Pyrazinyl NH—C(O) PyrazinylZ₁: F (para) Z₂: Cl (meta) CF₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: Cl (para)Z₂: F (meta) CF₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: CH₃ (para) CF₂Pyrazinyl NH—C(O) Pyrazinyl Z₁: CH₃ (meta) CF₂ Pyrazinyl NH—C(O)Pyrazinyl Z₁: CH₃ (ortho) CF₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: CH₂—CH₃(para) CF₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: CH₂—CH₃ (meta) CF₂ PyrazinylNH—C(O) Pyrazinyl Z₁: CH₂—CH₃ (ortho) CF₂ Pyrazinyl NH—C(O) PyrazinylZ₁: CH₂—CH₂—CH₃ or iPr (para) CF₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) CF₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: CH₂F(para) CF₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: CH₂F (meta) CF₂ PyrazinylNH—C(O) Pyrazinyl Z₁: CH₂F (ortho) CF₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁:CHF₂ (para) CF₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: CHF₂ (meta) CF₂Pyrazinyl NH—C(O) Pyrazinyl Z₁: CHF₂ (ortho) CF₂ Pyrazinyl NH—C(O)Pyrazinyl Z₁: CF₃ (para) CF₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: CF₃ (meta)CF₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: CF₃ (ortho) CF₂ Pyrazinyl NH—C(O)Pyrazinyl Z₁: CH₂—CH₂F (para) CF₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁:CH₂—CH₂F (meta) CF₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: CH₂—CH₂F (ortho) CF₂Pyrazinyl NH—C(O) Pyrazinyl Z₁: CH₂—CHF₂ (para) CF₂ Pyrazinyl NH—C(O)Pyrazinyl Z₁: CH₂—CHF₂ (meta) CF₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁:CH₂—CHF₂ (ortho) CF₂ Pyrazinyl NH—C(O) Pyrazinyl Z₁: CH₂—CF₃ (para) CF₂Pyrazinyl NH—C(O) Pyrazinyl Z₁: CH₂—CF₃ (meta) CF₂ Pyrazinyl NH—C(O)Pyrazinyl Z₁: CH₂—CF₃ (ortho) CF₂ Pyrazinyl NH—C(O) Pyrrolyl None CF₂Pyrazinyl NH—C(O) Pyrrolyl Z₁: F (2) CF₂ Pyrazinyl NH—C(O) Pyrrolyl Z₁:F (3) CF₂ Pyrazinyl NH—C(O) Pyrrolyl Z₁: F (2) Z₂: F (3) CF₂ PyrazinylNH—C(O) Pyrrolyl Z₁: Cl (2) CF₂ Pyrazinyl NH—C(O) Pyrrolyl Z₁: Cl (3)CF₂ Pyrazinyl NH—C(O) Pyrrolyl Z₁: Cl (2) Z₂: Cl (3) CF₂ PyrazinylNH—C(O) Pyrrolyl Z₁: F (2) Z₂: Cl (3) CF₂ Pyrazinyl NH—C(O) Pyrrolyl Z₁:Cl (2) Z₂: F (3) CF₂ Pyrazinyl NH—C(O) Pyrrolyl Z₁: CH₃ (2) CF₂Pyrazinyl NH—C(O) Pyrrolyl Z₁: CH₃ (3) CF₂ Pyrazinyl NH—C(O) PyrrolylZ₁: CH₂—CH₃ (2) CF₂ Pyrazinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₃ (3) CF₂Pyrazinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂ PyrazinylNH—C(O) Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CF₂ Pyrazinyl NH—C(O)Pyrrolyl Z₁: CH₂F (2) CF₂ Pyrazinyl NH—C(O) Pyrrolyl Z₁: CH₂F (3) CF₂Pyrazinyl NH—C(O) Pyrrolyl Z₁: CHF₂ (2) CF₂ Pyrazinyl NH—C(O) PyrrolylZ₁: CHF₂ (3) CF₂ Pyrazinyl NH—C(O) Pyrrolyl Z₁: CF₃ (2) CF₂ PyrazinylNH—C(O) Pyrrolyl Z₁: CF₃ (3) CF₂ Pyrazinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₂F(2) CF₂ Pyrazinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₂F (3) CF₂ PyrazinylNH—C(O) Pyrrolyl Z₁: CH₂—CHF₂ (2) CF₂ Pyrazinyl NH—C(O) Pyrrolyl Z₁:CH₂—CHF₂ (3) CF₂ Pyrazinyl NH—C(O) Pyrrolyl Z₁: CH₂—CF₃ (2) CF₂Pyrazinyl NH—C(O) Pyrrolyl Z₁: CH₂—CF₃ (3) CF₂ Pyrazinyl NH—C(O)Imidazolyl None CF₂ Pyrazinyl NH—C(O) Imidazolyl Z₁: F (2) CF₂ PyrazinylNH—C(O) Imidazolyl Z₁: F (3) CF₂ Pyrazinyl NH—C(O) Imidazolyl Z₁: F (2)Z₂: F (3) CF₂ Pyrazinyl NH—C(O) Imidazolyl Z₁: Cl (2) CF₂ PyrazinylNH—C(O) Imidazolyl Z₁: Cl (3) CF₂ Pyrazinyl NH—C(O) Imidazolyl Z₁: Cl(2) Z₂: Cl (3) CF₂ Pyrazinyl NH—C(O) Imidazolyl Z₁: F (2) Z₂: Cl (3) CF₂Pyrazinyl NH—C(O) Imidazolyl Z₁: Cl (2) Z₂: F (3) CF₂ Pyrazinyl NH—C(O)Imidazolyl Z₁: CH₃ (2) CF₂ Pyrazinyl NH—C(O) Imidazolyl Z₁: CH₃ (3) CF₂Pyrazinyl NH—C(O) Imidazolyl Z₁: CH₂—CH₃ (2) CF₂ Pyrazinyl NH—C(O)Imidazolyl Z₁: CH₂—CH₃ (3) CF₂ Pyrazinyl NH—C(O) Imidazolyl Z₁:CH₂—CH₂—CH₃ or iPr (2) CF₂ Pyrazinyl NH—C(O) Imidazolyl Z₁: CH₂—CH₂—CH₃or iPr (3) CF₂ Pyrazinyl NH—C(O) Imidazolyl Z₁: CH₂F (2) CF₂ PyrazinylNH—C(O) Imidazolyl Z₁: CH₂F (3) CF₂ Pyrazinyl NH—C(O) Imidazolyl Z₁:CHF₂ (2) CF₂ Pyrazinyl NH—C(O) Imidazolyl Z₁: CHF₂ (3) CF₂ PyrazinylNH—C(O) Imidazolyl Z₁: CF₃ (2) CF₂ Pyrazinyl NH—C(O) Imidazolyl Z₁: CF₃(3) CF₂ Pyrazinyl NH—C(O) Imidazolyl Z₁: CH₂—CH₂F (2) CF₂ PyrazinylNH—C(O) Imidazolyl Z₁: CH₂—CH₂F (3) CF₂ Pyrazinyl NH—C(O) Imidazolyl Z₁:CH₂—CHF₂ (2) CF₂ Pyrazinyl NH—C(O) Imidazolyl Z₁: CH₂—CHF₂ (3) CF₂Pyrazinyl NH—C(O) Imidazolyl Z₁: CH₂—CF₃ (2) CF₂ Pyrazinyl NH—C(O)Imidazolyl Z₁: CH₂—CF₃ (3) CF₂ Pyrazinyl NH—C(O) Furanyl None CF₂Pyrazinyl NH—C(O) Furanyl Z₁: F (2) CF₂ Pyrazinyl NH—C(O) Furanyl Z₁: F(3) CF₂ Pyrazinyl NH—C(O) Furanyl Z₁: F (2) Z₂: F (3) CF₂ PyrazinylNH—C(O) Furanyl Z₁: Cl (2) CF₂ Pyrazinyl NH—C(O) Furanyl Z₁: Cl (3) CF₂Pyrazinyl NH—C(O) Furanyl Z₁: Cl (2) Z₂: Cl (3) CF₂ Pyrazinyl NH—C(O)Furanyl Z₁: F (2) Z₂: Cl (3) CF₂ Pyrazinyl NH—C(O) Furanyl Z₁: Cl (2)Z₂: F (3) CF₂ Pyrazinyl NH—C(O) Furanyl Z₁: CH₃ (2) CF₂ PyrazinylNH—C(O) Furanyl Z₁: CH₃ (3) CF₂ Pyrazinyl NH—C(O) Furanyl Z₁: CH₂—CH₃(2) CF₂ Pyrazinyl NH—C(O) Furanyl Z₁: CH₂—CH₃ (3) CF₂ Pyrazinyl NH—C(O)Furanyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂ Pyrazinyl NH—C(O) Furanyl Z₁:CH₂—CH₂—CH₃ or iPr (3) CF₂ Pyrazinyl NH—C(O) Furanyl Z₁: CH₂F (2) CF₂Pyrazinyl NH—C(O) Furanyl Z₁: CH₂F (3) CF₂ Pyrazinyl NH—C(O) Furanyl Z₁:CHF₂ (2) CF₂ Pyrazinyl NH—C(O) Furanyl Z₁: CHF₂ (3) CF₂ PyrazinylNH—C(O) Furanyl Z₁: CF₃ (2) CF₂ Pyrazinyl NH—C(O) Furanyl Z₁: CF₃ (3)CF₂ Pyrazinyl NH—C(O) Furanyl Z₁: CH₂—CH₂F (2) CF₂ Pyrazinyl NH—C(O)Furanyl Z₁: CH₂—CH₂F (3) CF₂ Pyrazinyl NH—C(O) Furanyl Z₁: CH₂—CHF₂ (2)CF₂ Pyrazinyl NH—C(O) Furanyl Z₁: CH₂—CHF₂ (3) CF₂ Pyrazinyl NH—C(O)Furanyl Z₁: CH₂—CF₃ (2) CF₂ Pyrazinyl NH—C(O) Furanyl Z₁: CH₂—CF₃ (3)CF₂ Pyrazinyl NH—C(O) Oxazolyl None CF₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: F(2) CF₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: F (3) CF₂ Pyrazinyl NH—C(O)Oxazolyl Z₁: F (2) Z₂: F (3) CF₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: Cl (2)CF₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: Cl (3) CF₂ Pyrazinyl NH—C(O) OxazolylZ₁: Cl (2) Z₂: Cl (3) CF₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: F (2) Z₂: Cl(3) CF₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: Cl (2) Z₂: F (3) CF₂ PyrazinylNH—C(O) Oxazolyl Z₁: CH₃ (2) CF₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: CH₃ (3)CF₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₃ (2) CF₂ Pyrazinyl NH—C(O)Oxazolyl Z₁: CH₂—CH₃ (3) CF₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₂—CH₃or iPr (2) CF₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CF₂Pyrazinyl NH—C(O) Oxazolyl Z₁: CH₂F (2) CF₂ Pyrazinyl NH—C(O) OxazolylZ₁: CH₂F (3) CF₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: CHF₂ (2) CF₂ PyrazinylNH—C(O) Oxazolyl Z₁: CHF₂ (3) CF₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: CF₃ (2)CF₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: CF₃ (3) CF₂ Pyrazinyl NH—C(O)Oxazolyl Z₁: CH₂—CH₂F (2) CF₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₂F(3) CF₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: CH₂—CHF₂ (2) CF₂ PyrazinylNH—C(O) Oxazolyl Z₁: CH₂—CHF₂ (3) CF₂ Pyrazinyl NH—C(O) Oxazolyl Z₁:CH₂—CF₃ (2) CF₂ Pyrazinyl NH—C(O) Oxazolyl Z₁: CH₂—CF₃ (3) CF₂ PyrazinylNH—C(O) Thiophenyl None CF₂ Pyrazinyl NH—C(O) Thiophenyl Z₁: F (2) CF₂Pyrazinyl NH—C(O) Thiophenyl Z₁: F (3) CF₂ Pyrazinyl NH—C(O) ThiophenylZ₁: F (2) Z₂: F (3) CF₂ Pyrazinyl NH—C(O) Thiophenyl Z₁: Cl (2) CF₂Pyrazinyl NH—C(O) Thiophenyl Z₁: Cl (3) CF₂ Pyrazinyl NH—C(O) ThiophenylZ₁: Cl (2) Z₂: Cl (3) CF₂ Pyrazinyl NH—C(O) Thiophenyl Z₁: F (2) Z₂: Cl(3) CF₂ Pyrazinyl NH—C(O) Thiophenyl Z₁: Cl (2) Z₂: F (3) CF₂ PyrazinylNH—C(O) Thiophenyl Z₁: CH₃ (2) CF₂ Pyrazinyl NH—C(O) Thiophenyl Z₁: CH₃(3) CF₂ Pyrazinyl NH—C(O) Thiophenyl Z₁: CH₂—CH₃ (2) CF₂ PyrazinylNH—C(O) Thiophenyl Z₁: CH₂—CH₃ (3) CF₂ Pyrazinyl NH—C(O) Thiophenyl Z₁:CH₂—CH₂—CH₃ or iPr (2) CF₂ Pyrazinyl NH—C(O) Thiophenyl Z₁: CH₂—CH₂—CH₃or iPr (3) CF₂ Pyrazinyl NH—C(O) Thiophenyl Z₁: CH₂F (2) CF₂ PyrazinylNH—C(O) Thiophenyl Z₁: CH₂F (3) CF₂ Pyrazinyl NH—C(O) Thiophenyl Z₁:CHF₂ (2) CF₂ Pyrazinyl NH—C(O) Thiophenyl Z₁: CHF₂ (3) CF₂ PyrazinylNH—C(O) Thiophenyl Z₁: CF₃ (2) CF₂ Pyrazinyl NH—C(O) Thiophenyl Z₁: CF₃(3) CF₂ Pyrazinyl NH—C(O) Thiophenyl Z₁: CH₂—CH₂F (2) CF₂ PyrazinylNH—C(O) Thiophenyl Z₁: CH₂—CH₂F (3) CF₂ Pyrazinyl NH—C(O) Thiophenyl Z₁:CH₂—CHF₂ (2) CF₂ Pyrazinyl NH—C(O) Thiophenyl Z₁: CH₂—CHF₂ (3) CF₂Pyrazinyl NH—C(O) Thiophenyl Z₁: CH₂—CF₃ (2) CF₂ Pyrazinyl NH—C(O)Thiophenyl Z₁: CH₂—CF₃ (3) CF₂ Pyrazinyl NH—C(O) Thiazolyl None CF₂Pyrazinyl NH—C(O) Thiazolyl Z₁: F (2) CF₂ Pyrazinyl NH—C(O) ThiazolylZ₁: F (3) CF₂ Pyrazinyl NH—C(O) Thiazolyl Z₁: F (2) Z₂: F (3) CF₂Pyrazinyl NH—C(O) Thiazolyl Z₁: Cl (2) CF₂ Pyrazinyl NH—C(O) ThiazolylZ₁: Cl (3) CF₂ Pyrazinyl NH—C(O) Thiazolyl Z₁: Cl (2) Z₂: Cl (3) CF₂Pyrazinyl NH—C(O) Thiazolyl Z₁: F (2) Z₂: Cl (3) CF₂ Pyrazinyl NH—C(O)Thiazolyl Z₁: Cl (2) Z₂: F (3) CF₂ Pyrazinyl NH—C(O) Thiazolyl Z₁: CH₃(2) CF₂ Pyrazinyl NH—C(O) Thiazolyl Z₁: CH₃ (3) CF₂ Pyrazinyl NH—C(O)Thiazolyl Z₁: CH₂—CH₃ (2) CF₂ Pyrazinyl NH—C(O) Thiazolyl Z₁: CH₂—CH₃(3) CF₂ Pyrazinyl NH—C(O) Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂Pyrazinyl NH—C(O) Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CF₂ PyrazinylNH—C(O) Thiazolyl Z₁: CH₂F (2) CF₂ Pyrazinyl NH—C(O) Thiazolyl Z₁: CH₂F(3) CF₂ Pyrazinyl NH—C(O) Thiazolyl Z₁: CHF₂ (2) CF₂ Pyrazinyl NH—C(O)Thiazolyl Z₁: CHF₂ (3) CF₂ Pyrazinyl NH—C(O) Thiazolyl Z₁: CF₃ (2) CF₂Pyrazinyl NH—C(O) Thiazolyl Z₁: CF₃ (3) CF₂ Pyrazinyl NH—C(O) ThiazolylZ₁: CH₂—CH₂F (2) CF₂ Pyrazinyl NH—C(O) Thiazolyl Z₁: CH₂—CH₂F (3) CF₂Pyrazinyl NH—C(O) Thiazolyl Z₁: CH₂—CHF₂ (2) CF₂ Pyrazinyl NH—C(O)Thiazolyl Z₁: CH₂—CHF₂ (3) CF₂ Pyrazinyl NH—C(O) Thiazolyl Z₁: CH₂—CF₃(2) CF₂ Pyrazinyl NH—C(O) Thiazolyl Z₁: CH₂—CF₃ (3) CF₂ Pyrazinyl NH—SO₂Phenyl None CF₂ Pyrazinyl NH—SO₂ Phenyl Z₁: F (para) CF₂ PyrazinylNH—SO₂ phenyl Z₁: F (meta) CF₂ Pyrazinyl NH—SO₂ phenyl Z₁: F (ortho) CF₂Pyrazinyl NH—SO₂ phenyl Z₁: F (para) Z₂: F (meta) CF₂ Pyrazinyl NH—SO₂Phenyl Z₁: Cl (meta) CF₂ Pyrazinyl NH—SO₂ Phenyl Z₁: Cl (para) CF₂Pyrazinyl NH—SO₂ Phenyl Z₁: Cl (para) Z₂: Cl (meta) CF₂ Pyrazinyl NH—SO₂Phenyl Z₁: F (para) Z₂: Cl (meta) CF₂ Pyrazinyl NH—SO₂ Phenyl Z₁: Cl(para) Z₂: F (meta) CF₂ Pyrazinyl NH—SO₂ Phenyl Z₁: CH₃ (para) CF₂Pyrazinyl NH—SO₂ Phenyl Z₁: CH₃ (meta) CF₂ Pyrazinyl NH—SO₂ Phenyl Z₁:CH₃ (ortho) CF₂ Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂—CH₃ (para) CF₂ PyrazinylNH—SO₂ Phenyl Z₁: CH₂—CH₃ (meta) CF₂ Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂—CH₃(ortho) CF₂ Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CF₂Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CF₂ PyrazinylNH—SO₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyrazinyl NH—SO₂ PhenylZ₁: CH₂F (para) CF₂ Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂F (meta) CF₂Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂F (ortho) CF₂ Pyrazinyl NH—SO₂ Phenyl Z₁:CHF₂ (para) CF₂ Pyrazinyl NH—SO₂ Phenyl Z₁: CHF₂ (meta) CF₂ PyrazinylNH—SO₂ Phenyl Z₁: CHF₂ (ortho) CF₂ Pyrazinyl NH—SO₂ Phenyl Z₁: CF₃(para) CF₂ Pyrazinyl NH—SO₂ Phenyl Z₁: CF₃ (meta) CF₂ Pyrazinyl NH—SO₂Phenyl Z₁: CF₃ (ortho) CF₂ Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂F (para)CF₂ Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂F (meta) CF₂ Pyrazinyl NH—SO₂Phenyl Z₁: CH₂—CH₂F (ortho) CF₂ Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂—CHF₂(para) CF₂ Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂—CHF₂ (meta) CF₂ PyrazinylNH—SO₂ Phenyl Z₁: CH₂—CHF₂ (ortho) CF₂ Pyrazinyl NH—SO₂ Phenyl Z₁:CH₂—CF₃ (para) CF₂ Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂—CF₃ (meta) CF₂Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂—CF₃ (ortho) CF₂ Pyrazinyl NH—SO₂Pyridinyl None CF₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: F (para) CF₂ PyrazinylNH—SO₂ Pyridinyl Z₁: F (meta) CF₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: F(ortho) CF₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: F (para) Z₂: F (meta) CF₂Pyrazinyl NH—SO₂ Pyridinyl Z₁: Cl (meta) CF₂ Pyrazinyl NH—SO₂ PyridinylZ₁: Cl (para) CF₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: Cl (para) Z₂: Cl (meta)CF₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: F (para) Z₂: Cl (meta) CF₂ PyrazinylNH—SO₂ Pyridinyl Z₁: Cl (para) Z₂: F (meta) CF₂ Pyrazinyl NH—SO₂Pyridinyl Z₁: CH₃ (para) CF₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₃ (meta)CF₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₃ (ortho) CF₂ Pyrazinyl NH—SO₂Pyridinyl Z₁: CH₂—CH₃ (para) CF₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₃(meta) CF₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₃ (ortho) CF₂ PyrazinylNH—SO₂ Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CF₂ Pyrazinyl NH—SO₂Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CF₂ Pyrazinyl NH—SO₂ PyridinylZ₁: CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₂F(para) CF₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₂F (meta) CF₂ PyrazinylNH—SO₂ Pyridinyl Z₁: CH₂F (ortho) CF₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁:CHF₂ (para) CF₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: CHF₂ (meta) CF₂ PyrazinylNH—SO₂ Pyridinyl Z₁: CHF₂ (ortho) CF₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: CF₃(para) CF₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: CF₃ (meta) CF₂ PyrazinylNH—SO₂ Pyridinyl Z₁: CF₃ (ortho) CF₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁:CH₂—CH₂F (para) CF₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₂F (meta) CF₂Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₂F (ortho) CF₂ Pyrazinyl NH—SO₂Pyridinyl Z₁: CH₂—CHF₂ (para) CF₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁:CH₂—CHF₂ (meta) CF₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₂—CHF₂ (ortho) CF₂Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₂—CF₃ (para) CF₂ Pyrazinyl NH—SO₂Pyridinyl Z₁: CH₂—CF₃ (meta) CF₂ Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₂—CF₃(ortho) CF₂ Pyrazinyl NH—SO₂ Pyrimidinyl None CF₂ Pyrazinyl NH—SO₂Pyrimidinyl Z₁: F (para) CF₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: F (meta)CF₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: F (ortho) CF₂ Pyrazinyl NH—SO₂Pyrimidinyl Z₁: F (para) Z₂: F (meta) CF₂ Pyrazinyl NH—SO₂ PyrimidinylZ₁: Cl (meta) CF₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: Cl (para) CF₂Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: Cl (para) Z₂: Cl (meta) CF₂ PyrazinylNH—SO₂ Pyrimidinyl Z₁: F (para) Z₂: Cl (meta) CF₂ Pyrazinyl NH—SO₂Pyrimidinyl Z₁: Cl (para) Z₂: F (meta) CF₂ Pyrazinyl NH—SO₂ PyrimidinylZ₁: CH₃ (para) CF₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₃ (meta) CF₂Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₃ (ortho) CF₂ Pyrazinyl NH—SO₂Pyrimidinyl Z₁: CH₂—CH₃ (para) CF₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁:CH₂—CH₃ (meta) CF₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₃ (ortho) CF₂Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CF₂ PyrazinylNH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CF₂ Pyrazinyl NH—SO₂Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyrazinyl NH—SO₂Pyrimidinyl Z₁: CH₂F (para) CF₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₂F(meta) CF₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₂F (ortho) CF₂ PyrazinylNH—SO₂ Pyrimidinyl Z₁: CHF₂ (para) CF₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁:CHF₂ (meta) CF₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CHF₂ (ortho) CF₂Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CF₃ (para) CF₂ Pyrazinyl NH—SO₂Pyrimidinyl Z₁: CF₃ (meta) CF₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CF₃(ortho) CF₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂F (para) CF₂Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂F (meta) CF₂ Pyrazinyl NH—SO₂Pyrimidinyl Z₁: CH₂—CH₂F (ortho) CF₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁:CH₂—CHF₂ (para) CF₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CHF₂ (meta) CF₂Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CHF₂ (ortho) CF₂ Pyrazinyl NH—SO₂Pyrimidinyl Z₁: CH₂—CF₃ (para) CF₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁:CH₂—CF₃ (meta) CF₂ Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CF₃ (ortho) CF₂Pyrazinyl NH—SO₂ Pyrazinyl None CF₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: F(para) CF₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: F (meta) CF₂ Pyrazinyl NH—SO₂Pyrazinyl Z₁: F (ortho) CF₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: F (para) Z₂:F (meta) CF₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: Cl (meta) CF₂ PyrazinylNH—SO₂ Pyrazinyl Z₁: Cl (para) CF₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: Cl(para) Z₂: Cl (meta) CF₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: F (para) Z₂: Cl(meta) CF₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: Cl (para) Z₂: F (meta) CF₂Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₃ (para) CF₂ Pyrazinyl NH—SO₂ PyrazinylZ₁: CH₃ (meta) CF₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₃ (ortho) CF₂Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₃ (para) CF₂ Pyrazinyl NH—SO₂Pyrazinyl Z₁: CH₂—CH₃ (meta) CF₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₃(ortho) CF₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) CF₂Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) CF₂ PyrazinylNH—SO₂ Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) CF₂ Pyrazinyl NH—SO₂Pyrazinyl Z₁: CH₂F (para) CF₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₂F (meta)CF₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₂F (ortho) CF₂ Pyrazinyl NH—SO₂Pyrazinyl Z₁: CHF₂ (para) CF₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CHF₂ (meta)CF₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CHF₂ (ortho) CF₂ Pyrazinyl NH—SO₂Pyrazinyl Z₁: CF₃ (para) CF₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CF₃ (meta)CF₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CF₃ (ortho) CF₂ Pyrazinyl NH—SO₂Pyrazinyl Z₁: CH₂—CH₂F (para) CF₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁:CH₂—CH₂F (meta) CF₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₂F (ortho) CF₂Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CHF₂ (para) CF₂ Pyrazinyl NH—SO₂Pyrazinyl Z₁: CH₂—CHF₂ (meta) CF₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁:CH₂—CHF₂ (ortho) CF₂ Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CF₃ (para) CF₂Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CF₃ (meta) CF₂ Pyrazinyl NH—SO₂Pyrazinyl Z₁: CH₂—CF₃ (ortho) CF₂ Pyrazinyl NH—SO₂ Pyrrolyl None CF₂Pyrazinyl NH—SO₂ Pyrrolyl Z₁: F (2) CF₂ Pyrazinyl NH—SO₂ Pyrrolyl Z₁: F(3) CF₂ Pyrazinyl NH—SO₂ Pyrrolyl Z₁: F (2) Z₂: F (3) CF₂ PyrazinylNH—SO₂ Pyrrolyl Z₁: Cl (2) CF₂ Pyrazinyl NH—SO₂ Pyrrolyl Z₁: Cl (3) CF₂Pyrazinyl NH—SO₂ Pyrrolyl Z₁: Cl (2) Z₂: Cl (3) CF₂ Pyrazinyl NH—SO₂Pyrrolyl Z₁: F (2) Z₂: Cl (3) CF₂ Pyrazinyl NH—SO₂ Pyrrolyl Z₁: Cl (2)Z₂: F (3) CF₂ Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CH₃ (2) CF₂ Pyrazinyl NH—SO₂Pyrrolyl Z₁: CH₃ (3) CF₂ Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CH₃ (2) CF₂Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CH₃ (3) CF₂ Pyrazinyl NH—SO₂ PyrrolylZ₁: CH₂—CH₂—CH₃ or iPr (2) CF₂ Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CH₂—CH₃or iPr (3) CF₂ Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CH₂F (2) CF₂ PyrazinylNH—SO₂ Pyrrolyl Z₁: CH₂F (3) CF₂ Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CHF₂ (2)CF₂ Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CHF₂ (3) CF₂ Pyrazinyl NH—SO₂ PyrrolylZ₁: CF₃ (2) CF₂ Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CF₃ (3) CF₂ PyrazinylNH—SO₂ Pyrrolyl Z₁: CH₂—CH₂F (2) CF₂ Pyrazinyl NH—SO₂ Pyrrolyl Z₁:CH₂—CH₂F (3) CF₂ Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CHF₂ (2) CF₂Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CHF₂ (3) CF₂ Pyrazinyl NH—SO₂ PyrrolylZ₁: CH₂—CF₃ (2) CF₂ Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CF₃ (3) CF₂Pyrazinyl NH—SO₂ Imidazolyl None CF₂ Pyrazinyl NH—SO₂ Imidazolyl Z₁: F(2) CF₂ Pyrazinyl NH—SO₂ Imidazolyl Z₁: F (3) CF₂ Pyrazinyl NH—SO₂Imidazolyl Z₁: F (2) Z₂: F (3) CF₂ Pyrazinyl NH—SO₂ Imidazolyl Z₁: Cl(2) CF₂ Pyrazinyl NH—SO₂ Imidazolyl Z₁: Cl (3) CF₂ Pyrazinyl NH—SO₂Imidazolyl Z₁: Cl (2) Z₂: Cl (3) CF₂ Pyrazinyl NH—SO₂ Imidazolyl Z₁: F(2) Z₂: Cl (3) CF₂ Pyrazinyl NH—SO₂ Imidazolyl Z₁: Cl (2) Z₂: F (3) CF₂Pyrazinyl NH—SO₂ Imidazolyl Z₁: CH₃ (2) CF₂ Pyrazinyl NH—SO₂ ImidazolylZ₁: CH₃ (3) CF₂ Pyrazinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₃ (2) CF₂Pyrazinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₃ (3) CF₂ Pyrazinyl NH—SO₂Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂ Pyrazinyl NH—SO₂ ImidazolylZ₁: CH₂—CH₂—CH₃ or iPr (3) CF₂ Pyrazinyl NH—SO₂ Imidazolyl Z₁: CH₂F (2)CF₂ Pyrazinyl NH—SO₂ Imidazolyl Z₁: CH₂F (3) CF₂ Pyrazinyl NH—SO₂Imidazolyl Z₁: CHF₂ (2) CF₂ Pyrazinyl NH—SO₂ Imidazolyl Z₁: CHF₂ (3) CF₂Pyrazinyl NH—SO₂ Imidazolyl Z₁: CF₃ (2) CF₂ Pyrazinyl NH—SO₂ ImidazolylZ₁: CF₃ (3) CF₂ Pyrazinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₂F (2) CF₂Pyrazinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₂F (3) CF₂ Pyrazinyl NH—SO₂Imidazolyl Z₁: CH₂—CHF₂ (2) CF₂ Pyrazinyl NH—SO₂ Imidazolyl Z₁: CH₂—CHF₂(3) CF₂ Pyrazinyl NH—SO₂ Imidazolyl Z₁: CH₂—CF₃ (2) CF₂ Pyrazinyl NH—SO₂Imidazolyl Z₁: CH₂—CF₃ (3) CF₂ Pyrazinyl NH—SO₂ Furanyl None CF₂Pyrazinyl NH—SO₂ Furanyl Z₁: F (2) CF₂ Pyrazinyl NH—SO₂ Furanyl Z₁: F(3) CF₂ Pyrazinyl NH—SO₂ Furanyl Z₁: F (2) Z₂: F (3) CF₂ PyrazinylNH—SO₂ Furanyl Z₁: Cl (2) CF₂ Pyrazinyl NH—SO₂ Furanyl Z₁: Cl (3) CF₂Pyrazinyl NH—SO₂ Furanyl Z₁: Cl (2) Z₂: Cl (3) CF₂ Pyrazinyl NH—SO₂Furanyl Z₁: F (2) Z₂: Cl (3) CF₂ Pyrazinyl NH—SO₂ Furanyl Z₁: Cl (2) Z₂:F (3) CF₂ Pyrazinyl NH—SO₂ Furanyl Z₁: CH₃ (2) CF₂ Pyrazinyl NH—SO₂Furanyl Z₁: CH₃ (3) CF₂ Pyrazinyl NH—SO₂ Furanyl Z₁: CH₂—CH₃ (2) CF₂Pyrazinyl NH—SO₂ Furanyl Z₁: CH₂—CH₃ (3) CF₂ Pyrazinyl NH—SO₂ FuranylZ₁: CH₂—CH₂—CH₃ or iPr (2) CF₂ Pyrazinyl NH—SO₂ Furanyl Z₁: CH₂—CH₂—CH₃or iPr (3) CF₂ Pyrazinyl NH—SO₂ Furanyl Z₁: CH₂F (2) CF₂ PyrazinylNH—SO₂ Furanyl Z₁: CH₂F (3) CF₂ Pyrazinyl NH—SO₂ Furanyl Z₁: CHF₂ (2)CF₂ Pyrazinyl NH—SO₂ Furanyl Z₁: CHF₂ (3) CF₂ Pyrazinyl NH—SO₂ FuranylZ₁: CF₃ (2) CF₂ Pyrazinyl NH—SO₂ Furanyl Z₁: CF₃ (3) CF₂ PyrazinylNH—SO₂ Furanyl Z₁: CH₂—CH₂F (2) CF₂ Pyrazinyl NH—SO₂ Furanyl Z₁:CH₂—CH₂F (3) CF₂ Pyrazinyl NH—SO₂ Furanyl Z₁: CH₂—CHF₂ (2) CF₂ PyrazinylNH—SO₂ Furanyl Z₁: CH₂—CHF₂ (3) CF₂ Pyrazinyl NH—SO₂ Furanyl Z₁: CH₂—CF₃(2) CF₂ Pyrazinyl NH—SO₂ Furanyl Z₁: CH₂—CF₃ (3) CF₂ Pyrazinyl NH—SO₂Oxazolyl None CF₂ Pyrazinyl NH—SO₂ Oxazolyl Z₁: F (2) CF₂ PyrazinylNH—SO₂ Oxazolyl Z₁: F (3) CF₂ Pyrazinyl NH—SO₂ Oxazolyl Z₁: F (2) Z₂: F(3) CF₂ Pyrazinyl NH—SO₂ Oxazolyl Z₁: Cl (2) CF₂ Pyrazinyl NH—SO₂Oxazolyl Z₁: Cl (3) CF₂ Pyrazinyl NH—SO₂ Oxazolyl Z₁: Cl (2) Z₂: Cl (3)CF₂ Pyrazinyl NH—SO₂ Oxazolyl Z₁: F (2) Z₂: Cl (3) CF₂ Pyrazinyl NH—SO₂Oxazolyl Z₁: Cl (2) Z₂: F (3) CF₂ Pyrazinyl NH—SO₂ Oxazolyl Z₁: CH₃ (2)CF₂ Pyrazinyl NH—SO₂ Oxazolyl Z₁: CH₃ (3) CF₂ Pyrazinyl NH—SO₂ OxazolylZ₁: CH₂—CH₃ (2) CF₂ Pyrazinyl NH—SO₂ Oxazolyl Z₁: CH₂—CH₃ (3) CF₂Pyrazinyl NH—SO₂ Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂ PyrazinylNH—SO₂ Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CF₂ Pyrazinyl NH—SO₂ OxazolylZ₁: CH₂F (2) CF₂ Pyrazinyl NH—SO₂ Oxazolyl Z₁: CH₂F (3) CF₂ PyrazinylNH—SO₂ Oxazolyl Z₁: CHF₂ (2) CF₂ Pyrazinyl NH—SO₂ Oxazolyl Z₁: CHF₂ (3)CF₂ Pyrazinyl NH—SO₂ Oxazolyl Z₁: CF₃ (2) CF₂ Pyrazinyl NH—SO₂ OxazolylZ₁: CF₃ (3) CF₂ Pyrazinyl NH—SO₂ Oxazolyl Z₁: CH₂—CH₂F (2) CF₂ PyrazinylNH—SO₂ Oxazolyl Z₁: CH₂—CH₂F (3) CF₂ Pyrazinyl NH—SO₂ Oxazolyl Z₁:CH₂—CHF₂ (2) CF₂ Pyrazinyl NH—SO₂ Oxazolyl Z₁: CH₂—CHF₂ (3) CF₂Pyrazinyl NH—SO₂ Oxazolyl Z₁: CH₂—CF₃ (2) CF₂ Pyrazinyl NH—SO₂ OxazolylZ₁: CH₂—CF₃ (3) CF₂ Pyrazinyl NH—SO₂ Thiophenyl None CF₂ PyrazinylNH—SO₂ Thiophenyl Z₁: F (2) CF₂ Pyrazinyl NH—SO₂ Thiophenyl Z₁: F (3)CF₂ Pyrazinyl NH—SO₂ Thiophenyl Z₁: F (2) Z₂: F (3) CF₂ Pyrazinyl NH—SO₂Thiophenyl Z₁: Cl (2) CF₂ Pyrazinyl NH—SO₂ Thiophenyl Z₁: Cl (3) CF₂Pyrazinyl NH—SO₂ Thiophenyl Z₁: Cl (2) Z₂: Cl (3) CF₂ Pyrazinyl NH—SO₂Thiophenyl Z₁: F (2) Z₂: Cl (3) CF₂ Pyrazinyl NH—SO₂ Thiophenyl Z₁: Cl(2) Z₂: F (3) CF₂ Pyrazinyl NH—SO₂ Thiophenyl Z₁: CH₃ (2) CF₂ PyrazinylNH—SO₂ Thiophenyl Z₁: CH₃ (3) CF₂ Pyrazinyl NH—SO₂ Thiophenyl Z₁:CH₂—CH₃ (2) CF₂ Pyrazinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₃ (3) CF₂Pyrazinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂ PyrazinylNH—SO₂ Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CF₂ Pyrazinyl NH—SO₂Thiophenyl Z₁: CH₂F (2) CF₂ Pyrazinyl NH—SO₂ Thiophenyl Z₁: CH₂F (3) CF₂Pyrazinyl NH—SO₂ Thiophenyl Z₁: CHF₂ (2) CF₂ Pyrazinyl NH—SO₂ ThiophenylZ₁: CHF₂ (3) CF₂ Pyrazinyl NH—SO₂ Thiophenyl Z₁: CF₃ (2) CF₂ PyrazinylNH—SO₂ Thiophenyl Z₁: CF₃ (3) CF₂ Pyrazinyl NH—SO₂ Thiophenyl Z₁:CH₂—CH₂F (2) CF₂ Pyrazinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₂F (3) CF₂Pyrazinyl NH—SO₂ Thiophenyl Z₁: CH₂—CHF₂ (2) CF₂ Pyrazinyl NH—SO₂Thiophenyl Z₁: CH₂—CHF₂ (3) CF₂ Pyrazinyl NH—SO₂ Thiophenyl Z₁: CH₂—CF₃(2) CF₂ Pyrazinyl NH—SO₂ Thiophenyl Z₁: CH₂—CF₃ (3) CF₂ Pyrazinyl NH—SO₂Thiazolyl None CF₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁: F (2) CF₂ PyrazinylNH—SO₂ Thiazolyl Z₁: F (3) CF₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁: F (2) Z₂:F (3) CF₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁: Cl (2) CF₂ Pyrazinyl NH—SO₂Thiazolyl Z₁: Cl (3) CF₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁: Cl (2) Z₂: Cl(3) CF₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁: F (2) Z₂: Cl (3) CF₂ PyrazinylNH—SO₂ Thiazolyl Z₁: Cl (2) Z₂: F (3) CF₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁:CH₃ (2) CF₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁: CH₃ (3) CF₂ Pyrazinyl NH—SO₂Thiazolyl Z₁: CH₂—CH₃ (2) CF₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₃ (3)CF₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) CF₂ PyrazinylNH—SO₂ Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) CF₂ Pyrazinyl NH—SO₂Thiazolyl Z₁: CH₂F (2) CF₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁: CH₂F (3) CF₂Pyrazinyl NH—SO₂ Thiazolyl Z₁: CHF₂ (2) CF₂ Pyrazinyl NH—SO₂ ThiazolylZ₁: CHF₂ (3) CF₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁: CF₃ (2) CF₂ PyrazinylNH—SO₂ Thiazolyl Z₁: CF₃ (3) CF₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₂F(2) CF₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₂F (3) CF₂ Pyrazinyl NH—SO₂Thiazolyl Z₁: CH₂—CHF₂ (2) CF₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁: CH₂—CHF₂(3) CF₂ Pyrazinyl NH—SO₂ Thiazolyl Z₁: CH₂—CF₃ (2) CF₂ Pyrazinyl NH—SO₂Thiazolyl Z₁: CH₂—CF₃ (3) S pyridinyl NH—CH₂ Phenyl None S pyridinylNH—CH₂ Phenyl Z₁: F (para) S pyridinyl NH—CH₂ phenyl Z₁: F (meta) Spyridinyl NH—CH₂ phenyl Z₁: F (ortho) S pyridinyl NH—CH₂ phenyl Z₁: F(para) Z₂: F (meta) S Pyridinyl NH—CH₂ Phenyl Z₁: Cl (meta) S PyridinylNH—CH₂ Phenyl Z₁: Cl (para) S Pyridinyl NH—CH₂ Phenyl Z₁: Cl (para) Z₂:Cl (meta) S Pyridinyl NH—CH₂ Phenyl Z₁: F (para) Z₂: Cl (meta) SPyridinyl NH—CH₂ Phenyl Z₁: Cl (para) Z₂: F (meta) S Pyridinyl NH—CH₂Phenyl Z₁: CH₃ (para) S Pyridinyl NH—CH₂ Phenyl Z₁: CH₃ (meta) SPyridinyl NH—CH₂ Phenyl Z₁: CH₃ (ortho) S Pyridinyl NH—CH₂ Phenyl Z₁:CH₂—CH₃ (para) S Pyridinyl NH—CH₂ Phenyl Z₁: CH₂—CH₃ (meta) S PyridinylNH—CH₂ Phenyl Z₁: CH₂—CH₃ (ortho) S Pyridinyl NH—CH₂ Phenyl Z₁:CH₂—CH₂—CH₃ or iPr (para) S Pyridinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂—CH₃ oriPr (meta) S Pyridinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) SPyridinyl NH—CH₂ Phenyl Z₁: CH₂F (para) S Pyridinyl NH—CH₂ Phenyl Z₁:CH₂F (meta) S Pyridinyl NH—CH₂ Phenyl Z₁: CH₂F (ortho) S PyridinylNH—CH₂ Phenyl Z₁: CHF₂ (para) S Pyridinyl NH—CH₂ Phenyl Z₁: CHF₂ (meta)S Pyridinyl NH—CH₂ Phenyl Z₁: CHF₂ (ortho) S Pyridinyl NH—CH₂ Phenyl Z₁:CF₃ (para) S Pyridinyl NH—CH₂ Phenyl Z₁: CF₃ (meta) S Pyridinyl NH—CH₂Phenyl Z₁: CF₃ (ortho) S Pyridinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂F (para) SPyridinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂F (meta) S Pyridinyl NH—CH₂ PhenylZ₁: CH₂—CH₂F (ortho) S Pyridinyl NH—CH₂ Phenyl Z₁: CH₂—CHF₂ (para) SPyridinyl NH—CH₂ Phenyl Z₁: CH₂—CHF₂ (meta) S Pyridinyl NH—CH₂ PhenylZ₁: CH₂—CHF₂ (ortho) S Pyridinyl NH—CH₂ Phenyl Z₁: CH₂—CF₃ (para) SPyridinyl NH—CH₂ Phenyl Z₁: CH₂—CF₃ (meta) S Pyridinyl NH—CH₂ Phenyl Z₁:CH₂—CF₃ (ortho) S pyridinyl NH—CH₂ Pyridinyl None S pyridinyl NH—CH₂Pyridinyl Z₁: F (para) S pyridinyl NH—CH₂ Pyridinyl Z₁: F (meta) Spyridinyl NH—CH₂ Pyridinyl Z₁: F (ortho) S pyridinyl NH—CH₂ PyridinylZ₁: F (para) Z₂: F (meta) S Pyridinyl NH—CH₂ Pyridinyl Z₁: Cl (meta) SPyridinyl NH—CH₂ Pyridinyl Z₁: Cl (para) S Pyridinyl NH—CH₂ PyridinylZ₁: Cl (para) Z₂: Cl (meta) S Pyridinyl NH—CH₂ Pyridinyl Z₁: F (para)Z₂: Cl (meta) S Pyridinyl NH—CH₂ Pyridinyl Z₁: Cl (para) Z₂: F (meta) SPyridinyl NH—CH₂ Pyridinyl Z₁: CH₃ (para) S Pyridinyl NH—CH₂ PyridinylZ₁: CH₃ (meta) S Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₃ (ortho) S PyridinylNH—CH₂ Pyridinyl Z₁: CH₂—CH₃ (para) S Pyridinyl NH—CH₂ Pyridinyl Z₁:CH₂—CH₃ (meta) S Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₃ (ortho) SPyridinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) S PyridinylNH—CH₂ Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) S Pyridinyl NH—CH₂Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) S Pyridinyl NH—CH₂ PyridinylZ₁: CH₂F (para) S Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₂F (meta) S PyridinylNH—CH₂ Pyridinyl Z₁: CH₂F (ortho) S Pyridinyl NH—CH₂ Pyridinyl Z₁: CHF₂(para) S Pyridinyl NH—CH₂ Pyridinyl Z₁: CHF₂ (meta) S Pyridinyl NH—CH₂Pyridinyl Z₁: CHF₂ (ortho) S Pyridinyl NH—CH₂ Pyridinyl Z₁: CF₃ (para) SPyridinyl NH—CH₂ Pyridinyl Z₁: CF₃ (meta) S Pyridinyl NH—CH₂ PyridinylZ₁: CF₃ (ortho) S Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₂F (para) SPyridinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₂F (meta) S Pyridinyl NH—CH₂Pyridinyl Z₁: CH₂—CH₂F (ortho) S Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₂—CHF₂(para) S Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₂—CHF₂ (meta) S PyridinylNH—CH₂ Pyridinyl Z₁: CH₂—CHF₂ (ortho) S Pyridinyl NH—CH₂ Pyridinyl Z₁:CH₂—CF₃ (para) S Pyridinyl NH—CH₂ Pyridinyl Z₁: CH₂—CF₃ (meta) SPyridinyl NH—CH₂ Pyridinyl Z₁: CH₂—CF₃ (ortho) S pyridinyl NH—CH₂Pyrimidinyl None S pyridinyl NH—CH₂ Pyrimidinyl Z₁: F (para) S pyridinylNH—CH₂ Pyrimidinyl Z₁: F (meta) S pyridinyl NH—CH₂ Pyrimidinyl Z₁: F(ortho) S pyridinyl NH—CH₂ Pyrimidinyl Z₁: F (para) Z₂: F (meta) SPyridinyl NH—CH₂ Pyrimidinyl Z₁: Cl (meta) S Pyridinyl NH—CH₂Pyrimidinyl Z₁: Cl (para) S Pyridinyl NH—CH₂ Pyrimidinyl Z₁: Cl (para)Z₂: Cl (meta) S Pyridinyl NH—CH₂ Pyrimidinyl Z₁: F (para) Z₂: Cl (meta)S Pyridinyl NH—CH₂ Pyrimidinyl Z₁: Cl (para) Z₂: F (meta) S PyridinylNH—CH₂ Pyrimidinyl Z₁: CH₃ (para) S Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₃(meta) S Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₃ (ortho) S Pyridinyl NH—CH₂Pyrimidinyl Z₁: CH₂—CH₃ (para) S Pyridinyl NH—CH₂ Pyrimidinyl Z₁:CH₂—CH₃ (meta) S Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₃ (ortho) SPyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) S PyridinylNH—CH₂ Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) S Pyridinyl NH—CH₂Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) S Pyridinyl NH—CH₂Pyrimidinyl Z₁: CH₂F (para) S Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₂F(meta) S Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₂F (ortho) S PyridinylNH—CH₂ Pyrimidinyl Z₁: CHF₂ (para) S Pyridinyl NH—CH₂ Pyrimidinyl Z₁:CHF₂ (meta) S Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CHF₂ (ortho) S PyridinylNH—CH₂ Pyrimidinyl Z₁: CF₃ (para) S Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CF₃(meta) S Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CF₃ (ortho) S Pyridinyl NH—CH₂Pyrimidinyl Z₁: CH₂—CH₂F (para) S Pyridinyl NH—CH₂ Pyrimidinyl Z₁:CH₂—CH₂F (meta) S Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₂F (ortho) SPyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CHF₂ (para) S Pyridinyl NH—CH₂Pyrimidinyl Z₁: CH₂—CHF₂ (meta) S Pyridinyl NH—CH₂ Pyrimidinyl Z₁:CH₂—CHF₂ (ortho) S Pyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CF₃ (para) SPyridinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CF₃ (meta) S Pyridinyl NH—CH₂Pyrimidinyl Z₁: CH₂—CF₃ (ortho) S pyridinyl NH—CH₂ Pyrazinyl None Spyridinyl NH—CH₂ Pyrazinyl Z₁: F (para) S pyridinyl NH—CH₂ Pyrazinyl Z₁:F (meta) S pyridinyl NH—CH₂ Pyrazinyl Z₁: F (ortho) S pyridinyl NH—CH₂Pyrazinyl Z₁: F (para) Z₂: F (meta) S Pyridinyl NH—CH₂ Pyrazinyl Z₁: Cl(meta) S Pyridinyl NH—CH₂ Pyrazinyl Z₁: Cl (para) S Pyridinyl NH—CH₂Pyrazinyl Z₁: Cl (para) Z₂: Cl (meta) S Pyridinyl NH—CH₂ Pyrazinyl Z₁: F(para) Z₂: Cl (meta) S Pyridinyl NH—CH₂ Pyrazinyl Z₁: Cl (para) Z₂: F(meta) S Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₃ (para) S Pyridinyl NH—CH₂Pyrazinyl Z₁: CH₃ (meta) S Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₃ (ortho) SPyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₃ (para) S Pyridinyl NH—CH₂Pyrazinyl Z₁: CH₂—CH₃ (meta) S Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₃(ortho) S Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) SPyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) S PyridinylNH—CH₂ Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) S Pyridinyl NH—CH₂Pyrazinyl Z₁: CH₂F (para) S Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂F (meta) SPyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂F (ortho) S Pyridinyl NH—CH₂ PyrazinylZ₁: CHF₂ (para) S Pyridinyl NH—CH₂ Pyrazinyl Z₁: CHF₂ (meta) S PyridinylNH—CH₂ Pyrazinyl Z₁: CHF₂ (ortho) S Pyridinyl NH—CH₂ Pyrazinyl Z₁: CF₃(para) S Pyridinyl NH—CH₂ Pyrazinyl Z₁: CF₃ (meta) S Pyridinyl NH—CH₂Pyrazinyl Z₁: CF₃ (ortho) S Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₂F(para) S Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₂F (meta) S PyridinylNH—CH₂ Pyrazinyl Z₁: CH₂—CH₂F (ortho) S Pyridinyl NH—CH₂ Pyrazinyl Z₁:CH₂—CHF₂ (para) S Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CHF₂ (meta) SPyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CHF₂ (ortho) S Pyridinyl NH—CH₂Pyrazinyl Z₁: CH₂—CF₃ (para) S Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CF₃(meta) S Pyridinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CF₃ (ortho) S pyridinylNH—CH₂ Pyrrolyl None S pyridinyl NH—CH₂ Pyrrolyl Z₁: F (2) S pyridinylNH—CH₂ Pyrrolyl Z₁: F (3) S pyridinyl NH—CH₂ Pyrrolyl Z₁: F (2) Z₂: F(3) S Pyridinyl NH—CH₂ Pyrrolyl Z₁: Cl (2) S Pyridinyl NH—CH₂ PyrrolylZ₁: Cl (3) S Pyridinyl NH—CH₂ Pyrrolyl Z₁: Cl (2) Z₂: Cl (3) S PyridinylNH—CH₂ Pyrrolyl Z₁: F (2) Z₂: Cl (3) S Pyridinyl NH—CH₂ Pyrrolyl Z₁: Cl(2) Z₂: F (3) S Pyridinyl NH—CH₂ Pyrrolyl Z₁: CH₃ (2) S Pyridinyl NH—CH₂Pyrrolyl Z₁: CH₃ (3) S Pyridinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₃ (2) SPyridinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₃ (3) S Pyridinyl NH—CH₂ PyrrolylZ₁: CH₂—CH₂—CH₃ or iPr (2) S Pyridinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₂—CH₃or iPr (3) S Pyridinyl NH—CH₂ Pyrrolyl Z₁: CH₂F (2) S Pyridinyl NH—CH₂Pyrrolyl Z₁: CH₂F (3) S Pyridinyl NH—CH₂ Pyrrolyl Z₁: CHF₂ (2) SPyridinyl NH—CH₂ Pyrrolyl Z₁: CHF₂ (3) S Pyridinyl NH—CH₂ Pyrrolyl Z₁:CF₃ (2) S Pyridinyl NH—CH₂ Pyrrolyl Z₁: CF₃ (3) S Pyridinyl NH—CH₂Pyrrolyl Z₁: CH₂—CH₂F (2) S Pyridinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₂F (3) SPyridinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CHF₂ (2) S Pyridinyl NH—CH₂ PyrrolylZ₁: CH₂—CHF₂ (3) S Pyridinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CF₃ (2) S PyridinylNH—CH₂ Pyrrolyl Z₁: CH₂—CF₃ (3) S pyridinyl NH—CH₂ Imidazolyl None Spyridinyl NH—CH₂ Imidazolyl Z₁: F (2) S pyridinyl NH—CH₂ Imidazolyl Z₁:F (3) S pyridinyl NH—CH₂ Imidazolyl Z₁: F (2) Z₂: F (3) S PyridinylNH—CH₂ Imidazolyl Z₁: Cl (2) S Pyridinyl NH—CH₂ Imidazolyl Z₁: Cl (3) SPyridinyl NH—CH₂ Imidazolyl Z₁: Cl (2) Z₂: Cl (3) S Pyridinyl NH—CH₂Imidazolyl Z₁: F (2) Z₂: Cl (3) S Pyridinyl NH—CH₂ Imidazolyl Z₁: Cl (2)Z₂: F (3) S Pyridinyl NH—CH₂ Imidazolyl Z₁: CH₃ (2) S Pyridinyl NH—CH₂Imidazolyl Z₁: CH₃ (3) S Pyridinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₃ (2) SPyridinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₃ (3) S Pyridinyl NH—CH₂Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) S Pyridinyl NH—CH₂ Imidazolyl Z₁:CH₂—CH₂—CH₃ or iPr (3) S Pyridinyl NH—CH₂ Imidazolyl Z₁: CH₂F (2) SPyridinyl NH—CH₂ Imidazolyl Z₁: CH₂F (3) S Pyridinyl NH—CH₂ ImidazolylZ₁: CHF₂ (2) S Pyridinyl NH—CH₂ Imidazolyl Z₁: CHF₂ (3) S PyridinylNH—CH₂ Imidazolyl Z₁: CF₃ (2) S Pyridinyl NH—CH₂ Imidazolyl Z₁: CF₃ (3)S Pyridinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₂F (2) S Pyridinyl NH—CH₂Imidazolyl Z₁: CH₂—CH₂F (3) S Pyridinyl NH—CH₂ Imidazolyl Z₁: CH₂—CHF₂(2) S Pyridinyl NH—CH₂ Imidazolyl Z₁: CH₂—CHF₂ (3) S Pyridinyl NH—CH₂Imidazolyl Z₁: CH₂—CF₃ (2) S Pyridinyl NH—CH₂ Imidazolyl Z₁: CH₂—CF₃ (3)S pyridinyl NH—CH₂ Furanyl None S pyridinyl NH—CH₂ Furanyl Z₁: F (2) Spyridinyl NH—CH₂ Furanyl Z₁: F (3) S pyridinyl NH—CH₂ Furanyl Z₁: F (2)Z₂: F (3) S Pyridinyl NH—CH₂ Furanyl Z₁: Cl (2) S Pyridinyl NH—CH₂Furanyl Z₁: Cl (3) S Pyridinyl NH—CH₂ Furanyl Z₁: Cl (2) Z₂: Cl (3) SPyridinyl NH—CH₂ Furanyl Z₁: F (2) Z₂: Cl (3) S Pyridinyl NH—CH₂ FuranylZ₁: Cl (2) Z₂: F (3) S Pyridinyl NH—CH₂ Furanyl Z₁: CH₃ (2) S PyridinylNH—CH₂ Furanyl Z₁: CH₃ (3) S Pyridinyl NH—CH₂ Furanyl Z₁: CH₂—CH₃ (2) SPyridinyl NH—CH₂ Furanyl Z₁: CH₂—CH₃ (3) S Pyridinyl NH—CH₂ Furanyl Z₁:CH₂—CH₂—CH₃ or iPr (2) S Pyridinyl NH—CH₂ Furanyl Z₁: CH₂—CH₂—CH₃ or iPr(3) S Pyridinyl NH—CH₂ Furanyl Z₁: CH₂F (2) S Pyridinyl NH—CH₂ FuranylZ₁: CH₂F (3) S Pyridinyl NH—CH₂ Furanyl Z₁: CHF₂ (2) S Pyridinyl NH—CH₂Furanyl Z₁: CHF₂ (3) S Pyridinyl NH—CH₂ Furanyl Z₁: CF₃ (2) S PyridinylNH—CH₂ Furanyl Z₁: CF₃ (3) S Pyridinyl NH—CH₂ Furanyl Z₁: CH₂—CH₂F (2) SPyridinyl NH—CH₂ Furanyl Z₁: CH₂—CH₂F (3) S Pyridinyl NH—CH₂ Furanyl Z₁:CH₂—CHF₂ (2) S Pyridinyl NH—CH₂ Furanyl Z₁: CH₂—CHF₂ (3) S PyridinylNH—CH₂ Furanyl Z₁: CH₂—CF₃ (2) S Pyridinyl NH—CH₂ Furanyl Z₁: CH₂—CF₃(3) S pyridinyl NH—CH₂ Oxazolyl None S pyridinyl NH—CH₂ Oxazolyl Z₁: F(2) S pyridinyl NH—CH₂ Oxazolyl Z₁: F (3) S pyridinyl NH—CH₂ OxazolylZ₁: F (2) Z₂: F (3) S Pyridinyl NH—CH₂ Oxazolyl Z₁: Cl (2) S PyridinylNH—CH₂ Oxazolyl Z₁: Cl (3) S Pyridinyl NH—CH₂ Oxazolyl Z₁: Cl (2) Z₂: Cl(3) S Pyridinyl NH—CH₂ Oxazolyl Z₁: F (2) Z₂: Cl (3) S Pyridinyl NH—CH₂Oxazolyl Z₁: Cl (2) Z₂: F (3) S Pyridinyl NH—CH₂ Oxazolyl Z₁: CH₃ (2) SPyridinyl NH—CH₂ Oxazolyl Z₁: CH₃ (3) S Pyridinyl NH—CH₂ Oxazolyl Z₁:CH₂—CH₃ (2) S Pyridinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₃ (3) S PyridinylNH—CH₂ Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) S Pyridinyl NH—CH₂ OxazolylZ₁: CH₂—CH₂—CH₃ or iPr (3) S Pyridinyl NH—CH₂ Oxazolyl Z₁: CH₂F (2) SPyridinyl NH—CH₂ Oxazolyl Z₁: CH₂F (3) S Pyridinyl NH—CH₂ Oxazolyl Z₁:CHF₂ (2) S Pyridinyl NH—CH₂ Oxazolyl Z₁: CHF₂ (3) S Pyridinyl NH—CH₂Oxazolyl Z₁: CF₃ (2) S Pyridinyl NH—CH₂ Oxazolyl Z₁: CF₃ (3) S PyridinylNH—CH₂ Oxazolyl Z₁: CH₂—CH₂F (2) S Pyridinyl NH—CH₂ Oxazolyl Z₁:CH₂—CH₂F (3) S Pyridinyl NH—CH₂ Oxazolyl Z₁: CH₂—CHF₂ (2) S PyridinylNH—CH₂ Oxazolyl Z₁: CH₂—CHF₂ (3) S Pyridinyl NH—CH₂ Oxazolyl Z₁: CH₂—CF₃(2) S Pyridinyl NH—CH₂ Oxazolyl Z₁: CH₂—CF₃ (3) S pyridinyl NH—CH₂Thiophenyl None S pyridinyl NH—CH₂ Thiophenyl Z₁: F (2) S pyridinylNH—CH₂ Thiophenyl Z₁: F (3) S pyridinyl NH—CH₂ Thiophenyl Z₁: F (2) Z₂:F (3) S Pyridinyl NH—CH₂ Thiophenyl Z₁: Cl (2) S Pyridinyl NH—CH₂Thiophenyl Z₁: Cl (3) S Pyridinyl NH—CH₂ Thiophenyl Z₁: Cl (2) Z₂: Cl(3) S Pyridinyl NH—CH₂ Thiophenyl Z₁: F (2) Z₂: Cl (3) S PyridinylNH—CH₂ Thiophenyl Z₁: Cl (2) Z₂: F (3) S Pyridinyl NH—CH₂ Thiophenyl Z₁:CH₃ (2) S Pyridinyl NH—CH₂ Thiophenyl Z₁: CH₃ (3) S Pyridinyl NH—CH₂Thiophenyl Z₁: CH₂—CH₃ (2) S Pyridinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₃ (3)S Pyridinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (2) S PyridinylNH—CH₂ Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (3) S Pyridinyl NH—CH₂Thiophenyl Z₁: CH₂F (2) S Pyridinyl NH—CH₂ Thiophenyl Z₁: CH₂F (3) SPyridinyl NH—CH₂ Thiophenyl Z₁: CHF₂ (2) S Pyridinyl NH—CH₂ ThiophenylZ₁: CHF₂ (3) S Pyridinyl NH—CH₂ Thiophenyl Z₁: CF₃ (2) S PyridinylNH—CH₂ Thiophenyl Z₁: CF₃ (3) S Pyridinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₂F(2) S Pyridinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₂F (3) S Pyridinyl NH—CH₂Thiophenyl Z₁: CH₂—CHF₂ (2) S Pyridinyl NH—CH₂ Thiophenyl Z₁: CH₂—CHF₂(3) S Pyridinyl NH—CH₂ Thiophenyl Z₁: CH₂—CF₃ (2) S Pyridinyl NH—CH₂Thiophenyl Z₁: CH₂—CF₃ (3) S pyridinyl NH—CH₂ Thiazolyl None S pyridinylNH—CH₂ Thiazolyl Z₁: F (2) S pyridinyl NH—CH₂ Thiazolyl Z₁: F (3) Spyridinyl NH—CH₂ Thiazolyl Z₁: F (2) Z₂: F (3) S Pyridinyl NH—CH₂Thiazolyl Z₁: Cl (2) S Pyridinyl NH—CH₂ Thiazolyl Z₁: Cl (3) S PyridinylNH—CH₂ Thiazolyl Z₁: Cl (2) Z₂: Cl (3) S Pyridinyl NH—CH₂ Thiazolyl Z₁:F (2) Z₂: Cl (3) S Pyridinyl NH—CH₂ Thiazolyl Z₁: Cl (2) Z₂: F (3) SPyridinyl NH—CH₂ Thiazolyl Z₁: CH₃ (2) S Pyridinyl NH—CH₂ Thiazolyl Z₁:CH₃ (3) S Pyridinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₃ (2) S Pyridinyl NH—CH₂Thiazolyl Z₁: CH₂—CH₃ (3) S Pyridinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₂—CH₃or iPr (2) S Pyridinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) SPyridinyl NH—CH₂ Thiazolyl Z₁: CH₂F (2) S Pyridinyl NH—CH₂ Thiazolyl Z₁:CH₂F (3) S Pyridinyl NH—CH₂ Thiazolyl Z₁: CHF₂ (2) S Pyridinyl NH—CH₂Thiazolyl Z₁: CHF₂ (3) S Pyridinyl NH—CH₂ Thiazolyl Z₁: CF₃ (2) SPyridinyl NH—CH₂ Thiazolyl Z₁: CF₃ (3) S Pyridinyl NH—CH₂ Thiazolyl Z₁:CH₂—CH₂F (2) S Pyridinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₂F (3) S PyridinylNH—CH₂ Thiazolyl Z₁: CH₂—CHF₂ (2) S Pyridinyl NH—CH₂ Thiazolyl Z₁:CH₂—CHF₂ (3) S Pyridinyl NH—CH₂ Thiazolyl Z₁: CH₂—CF₃ (2) S PyridinylNH—CH₂ Thiazolyl Z₁: CH₂—CF₃ (3) S pyridinyl NH—C(O) Phenyl None Spyridinyl NH—C(O) Phenyl Z₁: F (para) S pyridinyl NH—C(O) phenyl Z₁: F(meta) S pyridinyl NH—C(O) phenyl Z₁: F (ortho) S pyridinyl NH—C(O)phenyl Z₁: F (para) Z₂: F (meta) S Pyridinyl NH—C(O) Phenyl Z₁: Cl(meta) S Pyridinyl NH—C(O) Phenyl Z₁: Cl (para) S Pyridinyl NH—C(O)Phenyl Z₁: Cl (para) Z₂: Cl (meta) S Pyridinyl NH—C(O) Phenyl Z₁: F(para) Z₂: Cl (meta) S Pyridinyl NH—C(O) Phenyl Z₁: Cl (para) Z₂: F(meta) S Pyridinyl NH—C(O) Phenyl Z₁: CH₃ (para) S Pyridinyl NH—C(O)Phenyl Z₁: CH₃ (meta) S Pyridinyl NH—C(O) Phenyl Z₁: CH₃ (ortho) SPyridinyl NH—C(O) Phenyl Z₁: CH₂—CH₃ (para) S Pyridinyl NH—C(O) PhenylZ₁: CH₂—CH₃ (meta) S Pyridinyl NH—C(O) Phenyl Z₁: CH₂—CH₃ (ortho) SPyridinyl NH—C(O) Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (para) S PyridinylNH—C(O) Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) S Pyridinyl NH—C(O) PhenylZ₁: CH₂—CH₂—CH₃ or iPr (ortho) S Pyridinyl NH—C(O) Phenyl Z₁: CH₂F(para) S Pyridinyl NH—C(O) Phenyl Z₁: CH₂F (meta) S Pyridinyl NH—C(O)Phenyl Z₁: CH₂F (ortho) S Pyridinyl NH—C(O) Phenyl Z₁: CHF₂ (para) SPyridinyl NH—C(O) Phenyl Z₁: CHF₂ (meta) S Pyridinyl NH—C(O) Phenyl Z₁:CHF₂ (ortho) S Pyridinyl NH—C(O) Phenyl Z₁: CF₃ (para) S PyridinylNH—C(O) Phenyl Z₁: CF₃ (meta) S Pyridinyl NH—C(O) Phenyl Z₁: CF₃ (ortho)S Pyridinyl NH—C(O) Phenyl Z₁: CH₂—CH₂F (para) S Pyridinyl NH—C(O)Phenyl Z₁: CH₂—CH₂F (meta) S Pyridinyl NH—C(O) Phenyl Z₁: CH₂—CH₂F(ortho) S Pyridinyl NH—C(O) Phenyl Z₁: CH₂—CHF₂ (para) S PyridinylNH—C(O) Phenyl Z₁: CH₂—CHF₂ (meta) S Pyridinyl NH—C(O) Phenyl Z₁:CH₂—CHF₂ (ortho) S Pyridinyl NH—C(O) Phenyl Z₁: CH₂—CF₃ (para) SPyridinyl NH—C(O) Phenyl Z₁: CH₂—CF₃ (meta) S Pyridinyl NH—C(O) PhenylZ₁: CH₂—CF₃ (ortho) S pyridinyl NH—C(O) Pyridinyl None S pyridinylNH—C(O) Pyridinyl Z₁: F (para) S pyridinyl NH—C(O) Pyridinyl Z₁: F(meta) S pyridinyl NH—C(O) Pyridinyl Z₁: F (ortho) S pyridinyl NH—C(O)Pyridinyl Z₁: F (para) Z₂: F (meta) S Pyridinyl NH—C(O) Pyridinyl Z₁: Cl(meta) S Pyridinyl NH—C(O) Pyridinyl Z₁: Cl (para) S Pyridinyl NH—C(O)Pyridinyl Z₁: Cl (para) Z₂: Cl (meta) S Pyridinyl NH—C(O) Pyridinyl Z₁:F (para) Z₂: Cl (meta) S Pyridinyl NH—C(O) Pyridinyl Z₁: Cl (para) Z₂: F(meta) S Pyridinyl NH—C(O) Pyridinyl Z₁: CH₃ (para) S Pyridinyl NH—C(O)Pyridinyl Z₁: CH₃ (meta) S Pyridinyl NH—C(O) Pyridinyl Z₁: CH₃ (ortho) SPyridinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₃ (para) S Pyridinyl NH—C(O)Pyridinyl Z₁: CH₂—CH₃ (meta) S Pyridinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₃(ortho) S Pyridinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) SPyridinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) S PyridinylNH—C(O) Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) S Pyridinyl NH—C(O)Pyridinyl Z₁: CH₂F (para) S Pyridinyl NH—C(O) Pyridinyl Z₁: CH₂F (meta)S Pyridinyl NH—C(O) Pyridinyl Z₁: CH₂F (ortho) S Pyridinyl NH—C(O)Pyridinyl Z₁: CHF₂ (para) S Pyridinyl NH—C(O) Pyridinyl Z₁: CHF₂ (meta)S Pyridinyl NH—C(O) Pyridinyl Z₁: CHF₂ (ortho) S Pyridinyl NH—C(O)Pyridinyl Z₁: CF₃ (para) S Pyridinyl NH—C(O) Pyridinyl Z₁: CF₃ (meta) SPyridinyl NH—C(O) Pyridinyl Z₁: CF₃ (ortho) S Pyridinyl NH—C(O)Pyridinyl Z₁: CH₂—CH₂F (para) S Pyridinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₂F(meta) S Pyridinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₂F (ortho) S PyridinylNH—C(O) Pyridinyl Z₁: CH₂—CHF₂ (para) S Pyridinyl NH—C(O) Pyridinyl Z₁:CH₂—CHF₂ (meta) S Pyridinyl NH—C(O) Pyridinyl Z₁: CH₂—CHF₂ (ortho) SPyridinyl NH—C(O) Pyridinyl Z₁: CH₂—CF₃ (para) S Pyridinyl NH—C(O)Pyridinyl Z₁: CH₂—CF₃ (meta) S Pyridinyl NH—C(O) Pyridinyl Z₁: CH₂—CF₃(ortho) S pyridinyl NH—C(O) Pyrimidinyl None S pyridinyl NH—C(O)Pyrimidinyl Z₁: F (para) S pyridinyl NH—C(O) Pyrimidinyl Z₁: F (meta) Spyridinyl NH—C(O) Pyrimidinyl Z₁: F (ortho) S pyridinyl NH—C(O)Pyrimidinyl Z₁: F (para) Z₂: F (meta) S Pyridinyl NH—C(O) PyrimidinylZ₁: Cl (meta) S Pyridinyl NH—C(O) Pyrimidinyl Z₁: Cl (para) S PyridinylNH—C(O) Pyrimidinyl Z₁: Cl (para) Z₂: Cl (meta) S Pyridinyl NH—C(O)Pyrimidinyl Z₁: F (para) Z₂: Cl (meta) S Pyridinyl NH—C(O) PyrimidinylZ₁: Cl (para) Z₂: F (meta) S Pyridinyl NH—C(O) Pyrimidinyl Z₁: CH₃(para) S Pyridinyl NH—C(O) Pyrimidinyl Z₁: CH₃ (meta) S PyridinylNH—C(O) Pyrimidinyl Z₁: CH₃ (ortho) S Pyridinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CH₃ (para) S Pyridinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CH₃ (meta) SPyridinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CH₃ (ortho) S Pyridinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) S Pyridinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) S Pyridinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) S Pyridinyl NH—C(O)Pyrimidinyl Z₁: CH₂F (para) S Pyridinyl NH—C(O) Pyrimidinyl Z₁: CH₂F(meta) S Pyridinyl NH—C(O) Pyrimidinyl Z₁: CH₂F (ortho) S PyridinylNH—C(O) Pyrimidinyl Z₁: CHF₂ (para) S Pyridinyl NH—C(O) Pyrimidinyl Z₁:CHF₂ (meta) S Pyridinyl NH—C(O) Pyrimidinyl Z₁: CHF₂ (ortho) S PyridinylNH—C(O) Pyrimidinyl Z₁: CF₃ (para) S Pyridinyl NH—C(O) Pyrimidinyl Z₁:CF₃ (meta) S Pyridinyl NH—C(O) Pyrimidinyl Z₁: CF₃ (ortho) S PyridinylNH—C(O) Pyrimidinyl Z₁: CH₂—CH₂F (para) S Pyridinyl NH—C(O) PyrimidinylZ₁: CH₂—CH₂F (meta) S Pyridinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CH₂F (ortho)S Pyridinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CHF₂ (para) S Pyridinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CHF₂ (meta) S Pyridinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CHF₂ (ortho) S Pyridinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CF₃ (para) SPyridinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CF₃ (meta) S Pyridinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CF₃ (ortho) S pyridinyl NH—C(O) Pyrazinyl None Spyridinyl NH—C(O) Pyrazinyl Z₁: F (para) S pyridinyl NH—C(O) PyrazinylZ₁: F (meta) S pyridinyl NH—C(O) Pyrazinyl Z₁: F (ortho) S pyridinylNH—C(O) Pyrazinyl Z₁: F (para) Z₂: F (meta) S Pyridinyl NH—C(O)Pyrazinyl Z₁: Cl (meta) S Pyridinyl NH—C(O) Pyrazinyl Z₁: Cl (para) SPyridinyl NH—C(O) Pyrazinyl Z₁: Cl (para) Z₂: Cl (meta) S PyridinylNH—C(O) Pyrazinyl Z₁: F (para) Z₂: Cl (meta) S Pyridinyl NH—C(O)Pyrazinyl Z₁: Cl (para) Z₂: F (meta) S Pyridinyl NH—C(O) Pyrazinyl Z₁:CH₃ (para) S Pyridinyl NH—C(O) Pyrazinyl Z₁: CH₃ (meta) S PyridinylNH—C(O) Pyrazinyl Z₁: CH₃ (ortho) S Pyridinyl NH—C(O) Pyrazinyl Z₁:CH₂—CH₃ (para) S Pyridinyl NH—C(O) Pyrazinyl Z₁: CH₂—CH₃ (meta) SPyridinyl NH—C(O) Pyrazinyl Z₁: CH₂—CH₃ (ortho) S Pyridinyl NH—C(O)Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) S Pyridinyl NH—C(O) PyrazinylZ₁: CH₂—CH₂—CH₃ or iPr (meta) S Pyridinyl NH—C(O) Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) S Pyridinyl NH—C(O) Pyrazinyl Z₁: CH₂F (para)S Pyridinyl NH—C(O) Pyrazinyl Z₁: CH₂F (meta) S Pyridinyl NH—C(O)Pyrazinyl Z₁: CH₂F (ortho) S Pyridinyl NH—C(O) Pyrazinyl Z₁: CHF₂ (para)S Pyridinyl NH—C(O) Pyrazinyl Z₁: CHF₂ (meta) S Pyridinyl NH—C(O)Pyrazinyl Z₁: CHF₂ (ortho) S Pyridinyl NH—C(O) Pyrazinyl Z₁: CF₃ (para)S Pyridinyl NH—C(O) Pyrazinyl Z₁: CF₃ (meta) S Pyridinyl NH—C(O)Pyrazinyl Z₁: CF₃ (ortho) S Pyridinyl NH—C(O) Pyrazinyl Z₁: CH₂—CH₂F(para) S Pyridinyl NH—C(O) Pyrazinyl Z₁: CH₂—CH₂F (meta) S PyridinylNH—C(O) Pyrazinyl Z₁: CH₂—CH₂F (ortho) S Pyridinyl NH—C(O) Pyrazinyl Z₁:CH₂—CHF₂ (para) S Pyridinyl NH—C(O) Pyrazinyl Z₁: CH₂—CHF₂ (meta) SPyridinyl NH—C(O) Pyrazinyl Z₁: CH₂—CHF₂ (ortho) S Pyridinyl NH—C(O)Pyrazinyl Z₁: CH₂—CF₃ (para) S Pyridinyl NH—C(O) Pyrazinyl Z₁: CH₂—CF₃(meta) S Pyridinyl NH—C(O) Pyrazinyl Z₁: CH₂—CF₃ (ortho) S pyridinylNH—C(O) Pyrrolyl None S pyridinyl NH—C(O) Pyrrolyl Z₁: F (2) S pyridinylNH—C(O) Pyrrolyl Z₁: F (3) S pyridinyl NH—C(O) Pyrrolyl Z₁: F (2) Z₂: F(3) S Pyridinyl NH—C(O) Pyrrolyl Z₁: Cl (2) S Pyridinyl NH—C(O) PyrrolylZ₁: Cl (3) S Pyridinyl NH—C(O) Pyrrolyl Z₁: Cl (2) Z₂: Cl (3) SPyridinyl NH—C(O) Pyrrolyl Z₁: F (2) Z₂: Cl (3) S Pyridinyl NH—C(O)Pyrrolyl Z₁: Cl (2) Z₂: F (3) S Pyridinyl NH—C(O) Pyrrolyl Z₁: CH₃ (2) SPyridinyl NH—C(O) Pyrrolyl Z₁: CH₃ (3) S Pyridinyl NH—C(O) Pyrrolyl Z₁:CH₂—CH₃ (2) S Pyridinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₃ (3) S PyridinylNH—C(O) Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) S Pyridinyl NH—C(O) PyrrolylZ₁: CH₂—CH₂—CH₃ or iPr (3) S Pyridinyl NH—C(O) Pyrrolyl Z₁: CH₂F (2) SPyridinyl NH—C(O) Pyrrolyl Z₁: CH₂F (3) S Pyridinyl NH—C(O) Pyrrolyl Z₁:CHF₂ (2) S Pyridinyl NH—C(O) Pyrrolyl Z₁: CHF₂ (3) S Pyridinyl NH—C(O)Pyrrolyl Z₁: CF₃ (2) S Pyridinyl NH—C(O) Pyrrolyl Z₁: CF₃ (3) SPyridinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₂F (2) S Pyridinyl NH—C(O) PyrrolylZ₁: CH₂—CH₂F (3) S Pyridinyl NH—C(O) Pyrrolyl Z₁: CH₂—CHF₂ (2) SPyridinyl NH—C(O) Pyrrolyl Z₁: CH₂—CHF₂ (3) S Pyridinyl NH—C(O) PyrrolylZ₁: CH₂—CF₃ (2) S Pyridinyl NH—C(O) Pyrrolyl Z₁: CH₂—CF₃ (3) S pyridinylNH—C(O) Imidazolyl None S pyridinyl NH—C(O) Imidazolyl Z₁: F (2) Spyridinyl NH—C(O) Imidazolyl Z₁: F (3) S pyridinyl NH—C(O) ImidazolylZ₁: F (2) Z₂: F (3) S Pyridinyl NH—C(O) Imidazolyl Z₁: Cl (2) SPyridinyl NH—C(O) Imidazolyl Z₁: Cl (3) S Pyridinyl NH—C(O) ImidazolylZ₁: Cl (2) Z₂: Cl (3) S Pyridinyl NH—C(O) Imidazolyl Z₁: F (2) Z₂: Cl(3) S Pyridinyl NH—C(O) Imidazolyl Z₁: Cl (2) Z₂: F (3) S PyridinylNH—C(O) Imidazolyl Z₁: CH₃ (2) S Pyridinyl NH—C(O) Imidazolyl Z₁: CH₃(3) S Pyridinyl NH—C(O) Imidazolyl Z₁: CH₂—CH₃ (2) S Pyridinyl NH—C(O)Imidazolyl Z₁: CH₂—CH₃ (3) S Pyridinyl NH—C(O) Imidazolyl Z₁:CH₂—CH₂—CH₃ or iPr (2) S Pyridinyl NH—C(O) Imidazolyl Z₁: CH₂—CH₂—CH₃ oriPr (3) S Pyridinyl NH—C(O) Imidazolyl Z₁: CH₂F (2) S Pyridinyl NH—C(O)Imidazolyl Z₁: CH₂F (3) S Pyridinyl NH—C(O) Imidazolyl Z₁: CHF₂ (2) SPyridinyl NH—C(O) Imidazolyl Z₁: CHF₂ (3) S Pyridinyl NH—C(O) ImidazolylZ₁: CF₃ (2) S Pyridinyl NH—C(O) Imidazolyl Z₁: CF₃ (3) S PyridinylNH—C(O) Imidazolyl Z₁: CH₂—CH₂F (2) S Pyridinyl NH—C(O) Imidazolyl Z₁:CH₂—CH₂F (3) S Pyridinyl NH—C(O) Imidazolyl Z₁: CH₂—CHF₂ (2) S PyridinylNH—C(O) Imidazolyl Z₁: CH₂—CHF₂ (3) S Pyridinyl NH—C(O) Imidazolyl Z₁:CH₂—CF₃ (2) S Pyridinyl NH—C(O) Imidazolyl Z₁: CH₂—CF₃ (3) S pyridinylNH—C(O) Furanyl None S pyridinyl NH—C(O) Furanyl Z₁: F (2) S pyridinylNH—C(O) Furanyl Z₁: F (3) S pyridinyl NH—C(O) Furanyl Z₁: F (2) Z₂: F(3) S Pyridinyl NH—C(O) Furanyl Z₁: Cl (2) S Pyridinyl NH—C(O) FuranylZ₁: Cl (3) S Pyridinyl NH—C(O) Furanyl Z₁: Cl (2) Z₂: Cl (3) S PyridinylNH—C(O) Furanyl Z₁: F (2) Z₂: Cl (3) S Pyridinyl NH—C(O) Furanyl Z₁: Cl(2) Z₂: F (3) S Pyridinyl NH—C(O) Furanyl Z₁: CH₃ (2) S PyridinylNH—C(O) Furanyl Z₁: CH₃ (3) S Pyridinyl NH—C(O) Furanyl Z₁: CH₂—CH₃ (2)S Pyridinyl NH—C(O) Furanyl Z₁: CH₂—CH₃ (3) S Pyridinyl NH—C(O) FuranylZ₁: CH₂—CH₂—CH₃ or iPr (2) S Pyridinyl NH—C(O) Furanyl Z₁: CH₂—CH₂—CH₃or iPr (3) S Pyridinyl NH—C(O) Furanyl Z₁: CH₂F (2) S Pyridinyl NH—C(O)Furanyl Z₁: CH₂F (3) S Pyridinyl NH—C(O) Furanyl Z₁: CHF₂ (2) SPyridinyl NH—C(O) Furanyl Z₁: CHF₂ (3) S Pyridinyl NH—C(O) Furanyl Z₁:CF₃ (2) S Pyridinyl NH—C(O) Furanyl Z₁: CF₃ (3) S Pyridinyl NH—C(O)Furanyl Z₁: CH₂—CH₂F (2) S Pyridinyl NH—C(O) Furanyl Z₁: CH₂—CH₂F (3) SPyridinyl NH—C(O) Furanyl Z₁: CH₂—CHF₂ (2) S Pyridinyl NH—C(O) FuranylZ₁: CH₂—CHF₂ (3) S Pyridinyl NH—C(O) Furanyl Z₁: CH₂—CF₃ (2) S PyridinylNH—C(O) Furanyl Z₁: CH₂—CF₃ (3) S pyridinyl NH—C(O) Oxazolyl None Spyridinyl NH—C(O) Oxazolyl Z₁: F (2) S pyridinyl NH—C(O) Oxazolyl Z₁: F(3) S pyridinyl NH—C(O) Oxazolyl Z₁: F (2) Z₂: F (3) S Pyridinyl NH—C(O)Oxazolyl Z₁: Cl (2) S Pyridinyl NH—C(O) Oxazolyl Z₁: Cl (3) S PyridinylNH—C(O) Oxazolyl Z₁: Cl (2) Z₂: Cl (3) S Pyridinyl NH—C(O) Oxazolyl Z₁:F (2) Z₂: Cl (3) S Pyridinyl NH—C(O) Oxazolyl Z₁: Cl (2) Z₂: F (3) SPyridinyl NH—C(O) Oxazolyl Z₁: CH₃ (2) S Pyridinyl NH—C(O) Oxazolyl Z₁:CH₃ (3) S Pyridinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₃ (2) S Pyridinyl NH—C(O)Oxazolyl Z₁: CH₂—CH₃ (3) S Pyridinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₂—CH₃ oriPr (2) S Pyridinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) SPyridinyl NH—C(O) Oxazolyl Z₁: CH₂F (2) S Pyridinyl NH—C(O) Oxazolyl Z₁:CH₂F (3) S Pyridinyl NH—C(O) Oxazolyl Z₁: CHF₂ (2) S Pyridinyl NH—C(O)Oxazolyl Z₁: CHF₂ (3) S Pyridinyl NH—C(O) Oxazolyl Z₁: CF₃ (2) SPyridinyl NH—C(O) Oxazolyl Z₁: CF₃ (3) S Pyridinyl NH—C(O) Oxazolyl Z₁:CH₂—CH₂F (2) S Pyridinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₂F (3) S PyridinylNH—C(O) Oxazolyl Z₁: CH₂—CHF₂ (2) S Pyridinyl NH—C(O) Oxazolyl Z₁:CH₂—CHF₂ (3) S Pyridinyl NH—C(O) Oxazolyl Z₁: CH₂—CF₃ (2) S PyridinylNH—C(O) Oxazolyl Z₁: CH₂—CF₃ (3) S pyridinyl NH—C(O) Thiophenyl None Spyridinyl NH—C(O) Thiophenyl Z₁: F (2) S pyridinyl NH—C(O) ThiophenylZ₁: F (3) S pyridinyl NH—C(O) Thiophenyl Z₁: F (2) Z₂: F (3) S PyridinylNH—C(O) Thiophenyl Z₁: Cl (2) S Pyridinyl NH—C(O) Thiophenyl Z₁: Cl (3)S Pyridinyl NH—C(O) Thiophenyl Z₁: Cl (2) Z₂: Cl (3) S Pyridinyl NH—C(O)Thiophenyl Z₁: F (2) Z₂: Cl (3) S Pyridinyl NH—C(O) Thiophenyl Z₁: Cl(2) Z₂: F (3) S Pyridinyl NH—C(O) Thiophenyl Z₁: CH₃ (2) S PyridinylNH—C(O) Thiophenyl Z₁: CH₃ (3) S Pyridinyl NH—C(O) Thiophenyl Z₁:CH₂—CH₃ (2) S Pyridinyl NH—C(O) Thiophenyl Z₁: CH₂—CH₃ (3) S PyridinylNH—C(O) Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (2) S Pyridinyl NH—C(O)Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (3) S Pyridinyl NH—C(O) Thiophenyl Z₁:CH₂F (2) S Pyridinyl NH—C(O) Thiophenyl Z₁: CH₂F (3) S Pyridinyl NH—C(O)Thiophenyl Z₁: CHF₂ (2) S Pyridinyl NH—C(O) Thiophenyl Z₁: CHF₂ (3) SPyridinyl NH—C(O) Thiophenyl Z₁: CF₃ (2) S Pyridinyl NH—C(O) ThiophenylZ₁: CF₃ (3) S Pyridinyl NH—C(O) Thiophenyl Z₁: CH₂—CH₂F (2) S PyridinylNH—C(O) Thiophenyl Z₁: CH₂—CH₂F (3) S Pyridinyl NH—C(O) Thiophenyl Z₁:CH₂—CHF₂ (2) S Pyridinyl NH—C(O) Thiophenyl Z₁: CH₂—CHF₂ (3) S PyridinylNH—C(O) Thiophenyl Z₁: CH₂—CF₃ (2) S Pyridinyl NH—C(O) Thiophenyl Z₁:CH₂—CF₃ (3) S pyridinyl NH—C(O) Thiazolyl None S pyridinyl NH—C(O)Thiazolyl Z₁: F (2) S pyridinyl NH—C(O) Thiazolyl Z₁: F (3) S pyridinylNH—C(O) Thiazolyl Z₁: F (2) Z₂: F (3) S Pyridinyl NH—C(O) Thiazolyl Z₁:Cl (2) S Pyridinyl NH—C(O) Thiazolyl Z₁: Cl (3) S Pyridinyl NH—C(O)Thiazolyl Z₁: Cl (2) Z₂: Cl (3) S Pyridinyl NH—C(O) Thiazolyl Z₁: F (2)Z₂: Cl (3) S Pyridinyl NH—C(O) Thiazolyl Z₁: Cl (2) Z₂: F (3) SPyridinyl NH—C(O) Thiazolyl Z₁: CH₃ (2) S Pyridinyl NH—C(O) ThiazolylZ₁: CH₃ (3) S Pyridinyl NH—C(O) Thiazolyl Z₁: CH₂—CH₃ (2) S PyridinylNH—C(O) Thiazolyl Z₁: CH₂—CH₃ (3) S Pyridinyl NH—C(O) Thiazolyl Z₁:CH₂—CH₂—CH₃ or iPr (2) S Pyridinyl NH—C(O) Thiazolyl Z₁: CH₂—CH₂—CH₃ oriPr (3) S Pyridinyl NH—C(O) Thiazolyl Z₁: CH₂F (2) S Pyridinyl NH—C(O)Thiazolyl Z₁: CH₂F (3) S Pyridinyl NH—C(O) Thiazolyl Z₁: CHF₂ (2) SPyridinyl NH—C(O) Thiazolyl Z₁: CHF₂ (3) S Pyridinyl NH—C(O) ThiazolylZ₁: CF₃ (2) S Pyridinyl NH—C(O) Thiazolyl Z₁: CF₃ (3) S PyridinylNH—C(O) Thiazolyl Z₁: CH₂—CH₂F (2) S Pyridinyl NH—C(O) Thiazolyl Z₁:CH₂—CH₂F (3) S Pyridinyl NH—C(O) Thiazolyl Z₁: CH₂—CHF₂ (2) S PyridinylNH—C(O) Thiazolyl Z₁: CH₂—CHF₂ (3) S Pyridinyl NH—C(O) Thiazolyl Z₁:CH₂—CF₃ (2) S Pyridinyl NH—C(O) Thiazolyl Z₁: CH₂—CF₃ (3) S pyridinylNH—SO₂ Phenyl None S pyridinyl NH—SO₂ Phenyl Z₁: F (para) S pyridinylNH—SO₂ phenyl Z₁: F (meta) S pyridinyl NH—SO₂ phenyl Z₁: F (ortho) Spyridinyl NH—SO₂ phenyl Z₁: F (para) Z₂: F (meta) S Pyridinyl NH—SO₂Phenyl Z₁: Cl (meta) S Pyridinyl NH—SO₂ Phenyl Z₁: Cl (para) S PyridinylNH—SO₂ Phenyl Z₁: Cl (para) Z₂: Cl (meta) S Pyridinyl NH—SO₂ Phenyl Z₁:F (para) Z₁: Cl (meta) S Pyridinyl NH—SO₂ Phenyl Z₁: Cl (para) Z₁: F(meta) S Pyridinyl NH—SO₂ Phenyl Z₁: CH₃ (para) S Pyridinyl NH—SO₂Phenyl Z₁: CH₃ (meta) S Pyridinyl NH—SO₂ Phenyl Z₁: CH₃ (ortho) SPyridinyl NH—SO₂ Phenyl Z₁: CH₂—CH₃ (para) S Pyridinyl NH—SO₂ Phenyl Z₁:CH₂—CH₃ (meta) S Pyridinyl NH—SO₂ Phenyl Z₁: CH₂—CH₃ (ortho) S PyridinylNH—SO₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (para) S Pyridinyl NH—SO₂ PhenylZ₁: CH₂—CH₂—CH₃ or iPr (meta) S Pyridinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂—CH₃or iPr (ortho) S Pyridinyl NH—SO₂ Phenyl Z₁: CH₂F (para) S PyridinylNH—SO₂ Phenyl Z₁: CH₂F (meta) S Pyridinyl NH—SO₂ Phenyl Z₁: CH₂F (ortho)S Pyridinyl NH—SO₂ Phenyl Z₁: CHF₂ (para) S Pyridinyl NH—SO₂ Phenyl Z₁:CHF₂ (meta) S Pyridinyl NH—SO₂ Phenyl Z₁: CHF₂ (ortho) S PyridinylNH—SO₂ Phenyl Z₁: CF₃ (para) S Pyridinyl NH—SO₂ Phenyl Z₁: CF₃ (meta) SPyridinyl NH—SO₂ Phenyl Z₁: CF₃ (ortho) S Pyridinyl NH—SO₂ Phenyl Z₁:CH₂—CH₂F (para) S Pyridinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂F (meta) SPyridinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂F (ortho) S Pyridinyl NH—SO₂ PhenylZ₁: CH₂—CHF₂ (para) S Pyridinyl NH—SO₂ Phenyl Z₁: CH₂—CHF₂ (meta) SPyridinyl NH—SO₂ Phenyl Z₁: CH₂—CHF₂ (ortho) S Pyridinyl NH—SO₂ PhenylZ₁: CH₂—CF₃ (para) S Pyridinyl NH—SO₂ Phenyl Z₁: CH₂—CF₃ (meta) SPyridinyl NH—SO₂ Phenyl Z₁: CH₂—CF₃ (ortho) S pyridinyl NH—SO₂ PyridinylNone S pyridinyl NH—SO₂ Pyridinyl Z₁: F (para) S pyridinyl NH—SO₂Pyridinyl Z₁: F (meta) S pyridinyl NH—SO₂ Pyridinyl Z₁: F (ortho) Spyridinyl NH—SO₂ Pyridinyl Z₁: F (para) Z₂: F (meta) S Pyridinyl NH—SO₂Pyridinyl Z₁: Cl (meta) S Pyridinyl NH—SO₂ Pyridinyl Z₁: Cl (para) SPyridinyl NH—SO₂ Pyridinyl Z₁: Cl (para) Z₂: Cl (meta) S PyridinylNH—SO₂ Pyridinyl Z₁: F (para) Z₂: Cl (meta) S Pyridinyl NH—SO₂ PyridinylZ₁: Cl (para) Z₂: F (meta) S Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₃ (para) SPyridinyl NH—SO₂ Pyridinyl Z₁: CH₃ (meta) S Pyridinyl NH—SO₂ PyridinylZ₁: CH₃ (ortho) S Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₃ (para) SPyridinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₃ (meta) S Pyridinyl NH—SO₂Pyridinyl Z₁: CH₂—CH₃ (ortho) S Pyridinyl NH—SO₂ Pyridinyl Z₁:CH₂—CH₂—CH₃ or iPr (para) S Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₂—CH₃or iPr (meta) S Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr(ortho) S Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₂F (para) S Pyridinyl NH—SO₂Pyridinyl Z₁: CH₂F (meta) S Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₂F (ortho)S Pyridinyl NH—SO₂ Pyridinyl Z₁: CHF₂ (para) S Pyridinyl NH—SO₂Pyridinyl Z₁: CHF₂ (meta) S Pyridinyl NH—SO₂ Pyridinyl Z₁: CHF₂ (ortho)S Pyridinyl NH—SO₂ Pyridinyl Z₁: CF₃ (para) S Pyridinyl NH—SO₂ PyridinylZ₁: CF₃ (meta) S Pyridinyl NH—SO₂ Pyridinyl Z₁: CF₃ (ortho) S PyridinylNH—SO₂ Pyridinyl Z₁: CH₂—CH₂F (para) S Pyridinyl NH—SO₂ Pyridinyl Z₁:CH₂—CH₂F (meta) S Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₂F (ortho) SPyridinyl NH—SO₂ Pyridinyl Z₁: CH₂—CHF₂ (para) S Pyridinyl NH—SO₂Pyridinyl Z₁: CH₂—CHF₂ (meta) S Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₂—CHF₂(ortho) S Pyridinyl NH—SO₂ Pyridinyl Z₁: CH₂—CF₃ (para) S PyridinylNH—SO₂ Pyridinyl Z₁: CH₂—CF₃ (meta) S Pyridinyl NH—SO₂ Pyridinyl Z₁:CH₂—CF₃ (ortho) S pyridinyl NH—SO₂ Pyrimidinyl None S pyridinyl NH—SO₂Pyrimidinyl Z₁: F (para) S pyridinyl NH—SO₂ Pyrimidinyl Z₁: F (meta) Spyridinyl NH—SO₂ Pyrimidinyl Z₁: F (ortho) S pyridinyl NH—SO₂Pyrimidinyl Z₁: F (para) Z₂: F (meta) S Pyridinyl NH—SO₂ Pyrimidinyl Z₁:Cl (meta) S Pyridinyl NH—SO₂ Pyrimidinyl Z₁: Cl (para) S PyridinylNH—SO₂ Pyrimidinyl Z₁: Cl (para) Z₂: Cl (meta) S Pyridinyl NH—SO₂Pyrimidinyl Z₁: F (para) Z₂: Cl (meta) S Pyridinyl NH—SO₂ PyrimidinylZ₁: Cl (para) Z₂: F (meta) S Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₃ (para)S Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₃ (meta) S Pyridinyl NH—SO₂Pyrimidinyl Z₁: CH₃ (ortho) S Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₃(para) S Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₃ (meta) S PyridinylNH—SO₂ Pyrimidinyl Z₁: CH₂—CH₃ (ortho) S Pyridinyl NH—SO₂ PyrimidinylZ₁: CH₂—CH₂—CH₃ or iPr (para) S Pyridinyl NH—SO₂ Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) S Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂—CH₃or iPr (ortho) S Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₂F (para) SPyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₂F (meta) S Pyridinyl NH—SO₂Pyrimidinyl Z₁: CH₂F (ortho) S Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CHF₂(para) S Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CHF₂ (meta) S Pyridinyl NH—SO₂Pyrimidinyl Z₁: CHF₂ (ortho) S Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CF₃(para) S Pyridrnyl NH—SO₂ Pyrimidinyl Z₁: CF₃ (meta) S Pyridinyl NH—SO₂Pyrimidinyl Z₁: CF₃ (ortho) S Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂F(para) S Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂F (meta) S PyridinylNH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂F (ortho) S Pyridinyl NH—SO₂ PyrimidinylZ₁: CH₂—CHF₂ (para) S Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CHF₂ (meta) SPyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CHF₂ (ortho) S Pyridinyl NH—SO₂Pyrimidinyl Z₁: CH₂—CF₃ (para) S Pyridinyl NH—SO₂ Pyrimidinyl Z₁:CH₂—CF₃ (meta) S Pyridinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CF₃ (ortho) Spyridinyl NH—SO₂ Pyrazinyl None S pyridinyl NH—SO₂ Pyrazinyl Z₁: F(para) S pyridinyl NH—SO₂ Pyrazinyl Z₁: F (meta) S pyridinyl NH—SO₂Pyrazinyl Z₁: F (ortho) S pyridinyl NH—SO₂ Pyrazinyl Z₁: F (para) Z₂: F(meta) S Pyridinyl NH—SO₂ Pyrazinyl Z₁: Cl (meta) S Pyridinyl NH—SO₂Pyrazinyl Z₁: Cl (para) S Pyridinyl NH—SO₂ Pyrazinyl Z₁: Cl (para) Z₂:Cl (meta) S Pyridinyl NH—SO₂ Pyrazinyl Z₁: F (para) Z₂: Cl (meta) SPyridinyl NH—SO₂ Pyrazinyl Z₁: Cl (para) Z₂: F (meta) S Pyridinyl NH—SO₂Pyrazinyl Z₁: CH₃ (para) S Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₃ (meta) SPyridinyl NH—SO₂ Pyrazinyl Z₁: CH₃ (ortho) S Pyridinyl NH—SO₂ PyrazinylZ₁: CH₂—CH₃ (para) S Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₃ (meta) SPyridinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₃ (ortho) S Pyridinyl NH—SO₂Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) S Pyridinyl NH—SO₂ Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) S Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₂—CH₃or iPr (ortho) S Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₂F (para) S PyridinylNH—SO₂ Pyrazinyl Z₁: CH₂F (meta) S Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₂F(ortho) S Pyridinyl NH—SO₂ Pyrazinyl Z₁: CHF₂ (para) S Pyridinyl NH—SO₂Pyrazinyl Z₁: CHF₂ (meta) S Pyridinyl NH—SO₂ Pyrazinyl Z₁: CHF₂ (ortho)S Pyridinyl NH—SO₂ Pyrazinyl Z₁: CF₃ (para) S Pyridinyl NH—SO₂ PyrazinylZ₁: CF₃ (meta) S Pyridinyl NH—SO₂ Pyrazinyl Z₁: CF₃ (ortho) S PyridinylNH—SO₂ Pyrazinyl Z₁: CH₂—CH₂F (para) S Pyridinyl NH—SO₂ Pyrazinyl Z₁:CH₂—CH₂F (meta) S Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₂F (ortho) SPyridinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CHF₂ (para) S Pyridinyl NH—SO₂Pyrazinyl Z₁: CH₂—CHF₂ (meta) S Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CHF₂(ortho) S Pyridinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CF₃ (para) S PyridinylNH—SO₂ Pyrazinyl Z₁: CH₂—CF₃ (meta) S Pyridinyl NH—SO₂ Pyrazinyl Z₁:CH₂—CF₃ (ortho) S pyridinyl NH—SO₂ Pyrrolyl None S pyridinyl NH—SO₂Pyrrolyl Z₁: F (2) S pyridinyl NH—SO₂ Pyrrolyl Z₁: F (3) S pyridinylNH—SO₂ Pyrrolyl Z₁: F (2) Z₂: F (3) S Pyridinyl NH—SO₂ Pyrrolyl Z₁: Cl(2) S Pyridinyl NH—SO₂ Pyrrolyl Z₁: Cl (3) S Pyridinyl NH—SO₂ PyrrolylZ₁: Cl (2) Z₂: Cl (3) S Pyridinyl NH—SO₂ Pyrrolyl Z₁: F (2) Z₂: Cl (3) SPyridinyl NH—SO₂ Pyrrolyl Z₁: Cl (2) Z₂: F (3) S Pyridinyl NH—SO₂Pyrrolyl Z₁: CH₃ (2) S Pyridinyl NH—SO₂ Pyrrolyl Z₁: CH₃ (3) S PyridinylNH—SO₂ Pyrrolyl Z₁: CH₂—CH₃ (2) S Pyridinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CH₃(3) S Pyridinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) S PyridinylNH—SO₂ Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) S Pyridinyl NH—SO₂ PyrrolylZ₁: CH₂F (2) S Pyridinyl NH—SO₂ Pyrrolyl Z₁: CH₂F (3) S Pyridinyl NH—SO₂Pyrrolyl Z₁: CHF₂ (2) S Pyridinyl NH—SO₂ Pyrrolyl Z₁: CHF₂ (3) SPyridinyl NH—SO₂ Pyrrolyl Z₁: CF₃ (2) S Pyridinyl NH—SO₂ Pyrrolyl Z₁:CF₃ (3) S Pyridinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CH₂F (2) S Pyridinyl NH—SO₂Pyrrolyl Z₁: CH₂—CH₂F (3) S Pyridinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CHF₂ (2) SPyridinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CHF₂ (3) S Pyridinyl NH—SO₂ PyrrolylZ₁: CH₂—CF₃ (2) S Pyridinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CF₃ (3) S pyridinylNH—SO₂ Imidazolyl None S pyridinyl NH—SO₂ Imidazolyl Z₁: F (2) Spyridinyl NH—SO₂ Imidazolyl Z₁: F (3) S pyridinyl NH—SO₂ Imidazolyl Z₁:F (2) Z₂: F (3) S Pyridinyl NH—SO₂ Imidazolyl Z₁: Cl (2) S PyridinylNH—SO₂ Imidazolyl Z₁: Cl (3) S Pyridinyl NH—SO₂ Imidazolyl Z₁: Cl (2)Z₂: Cl (3) S Pyridinyl NH—SO₂ Imidazolyl Z₁: F (2) Z₂: Cl (3) SPyridinyl NH—SO₂ Imidazolyl Z₁: Cl (2) Z₂: F (3) S Pyridinyl NH—SO₂Imidazolyl Z₁: CH₃ (2) S Pyridinyl NH—SO₂ Imidazolyl Z₁: CH₃ (3) SPyridinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₃ (2) S Pyridinyl NH—SO₂Imidazolyl Z₁: CH₂—CH₃ (3) S Pyridinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₂—CH₃or iPr (2) S Pyridinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) SPyridinyl NH—SO₂ Imidazolyl Z₁: CH₂F (2) S Pyridinyl NH—SO₂ ImidazolylZ₁: CH₂F (3) S Pyridinyl NH—SO₂ Imidazolyl Z₁: CHF₂ (2) S PyridinylNH—SO₂ Imidazolyl Z₁: CHF₂ (3) S Pyridinyl NH—SO₂ Imidazolyl Z₁: CF₃ (2)S Pyridinyl NH—SO₂ Imidazolyl Z₁: CF₃ (3) S Pyridinyl NH—SO₂ ImidazolylZ₁: CH₂—CH₂F (2) S Pyridinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₂F (3) SPyridinyl NH—SO₂ Imidazolyl Z₁: CH₂—CHF₂ (2) S Pyridinyl NH—SO₂Imidazolyl Z₁: CH₂—CHF₂ (3) S Pyridinyl NH—SO₂ Imidazolyl Z₁: CH₂—CF₃(2) S Pyridinyl NH—SO₂ Imidazolyl Z₁: CH₂—CF₃ (3) S pyridinyl NH—SO₂Furanyl None S pyridinyl NH—SO₂ Furanyl Z₁: F (2) S pyridinyl NH—SO₂Furanyl Z₁: F (3) S pyridinyl NH—SO₂ Furanyl Z₁: F (2) Z₂: F (3) SPyridinyl NH—SO₂ Furanyl Z₁: Cl (2) S Pyridinyl NH—SO₂ Furanyl Z₁: Cl(3) S Pyridinyl NH—SO₂ Furanyl Z₁: Cl (2) Z₂: Cl (3) S Pyridinyl NH—SO₂Furanyl Z₁: F (2) Z₂: Cl (3) S Pyridinyl NH—SO₂ Furanyl Z₁: Cl (2) Z₂: F(3) S Pyridinyl NH—SO₂ Furanyl Z₁: CH₃ (2) S Pyridinyl NH—SO₂ FuranylZ₁: CH₃ (3) S Pyridinyl NH—SO₂ Furanyl Z₁: CH₂—CH₃ (2) S PyridinylNH—SO₂ Furanyl Z₁: CH₂—CH₃ (3) S Pyridinyl NH—SO₂ Furanyl Z₁:CH₂—CH₂—CH₃ or iPr (2) S Pyridinyl NH—SO₂ Furanyl Z₁: CH₂—CH₂—CH₃ or iPr(3) S Pyridinyl NH—SO₂ Furanyl Z₁: CH₂F (2) S Pyridinyl NH—SO₂ FuranylZ₁: CH₂F (3) S Pyridinyl NH—SO₂ Furanyl Z₁: CHF₂ (2) S Pyridinyl NH—SO₂Furanyl Z₁: CHF₂ (3) S Pyridinyl NH—SO₂ Furanyl Z₁: CF₃ (2) S PyridinylNH—SO₂ Furanyl Z₁: CF₃ (3) S Pyridinyl NH—SO₂ Furanyl Z₁: CH₂—CH₂F (2) SPyridinyl NH—SO₂ Furanyl Z₁: CH₂—CH₂F (3) S Pyridinyl NH—SO₂ Furanyl Z₁:CH₂—CHF₂ (2) S Pyridinyl NH—SO₂ Furanyl Z₁: CH₂—CHF₂ (3) S PyridinylNH—SO₂ Furanyl Z₁: CH₂—CF₃ (2) S Pyridinyl NH—SO₂ Furanyl Z₁: CH₂—CF₃(3) S pyridinyl NH—SO₂ Oxazolyl None S pyridinyl NH—SO₂ Oxazolyl Z₁: F(2) S pyridinyl NH—SO₂ Oxazolyl Z₁: F (3) S pyridinyl NH—SO₂ OxazolylZ₁: F (2) Z₂: F (3) S Pyridinyl NH—SO₂ Oxazolyl Z₁: Cl (2) S PyridinylNH—SO₂ Oxazolyl Z₁: Cl (3) S Pyridinyl NH—SO₂ Oxazolyl Z₁: Cl (2) Z₂: Cl(3) S Pyridinyl NH—SO₂ Oxazolyl Z₁: F (2) Z₂: Cl (3) S Pyridinyl NH—SO₂Oxazolyl Z₁: Cl (2) Z₂: F (3) S Pyridinyl NH—SO₂ Oxazolyl Z₁: CH₃ (2) SPyridinyl NH—SO₂ Oxazolyl Z₁: CH₃ (3) S Pyridinyl NH—SO₂ Oxazolyl Z₁:CH₂—CH₃ (2) S Pyridinyl NH—SO₂ Oxazolyl Z₁: CH₂—CH₃ (3) S PyridinylNH—SO₂ Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) S Pyridinyl NH—SO₂ OxazolylZ₁: CH₂—CH₂—CH₃ or iPr (3) S Pyridinyl NH—SO₂ Oxazolyl Z₁: CH₂F (2) SPyridinyl NH—SO₂ Oxazolyl Z₁: CH₂F (3) S Pyridinyl NH—SO₂ Oxazolyl Z₁:CHF₂ (2) S Pyridinyl NH—SO₂ Oxazolyl Z₁: CHF₂ (3) S Pyridinyl NH—SO₂Oxazolyl Z₁: CF₃ (2) S Pyridinyl NH—SO₂ Oxazolyl Z₁: CF₃ (3) S PyridinylNH—SO₂ Oxazolyl Z₁: CH₂—CH₂F (2) S Pyridinyl NH—SO₂ Oxazolyl Z₁:CH₂—CH₂F (3) S Pyridinyl NH—SO₂ Oxazolyl Z₁: CH₂—CHF₂ (2) S PyridinylNH—SO₂ Oxazolyl Z₁: CH₂—CHF₂ (3) S Pyridinyl NH—SO₂ Oxazolyl Z₁: CH₂—CF₃(2) S Pyridinyl NH—SO₂ Oxazolyl Z₁: CH₂—CF₃ (3) S pyridinyl NH—SO₂Thiophenyl None S pyridinyl NH—SO₂ Thiophenyl Z₁: F (2) S pyridinylNH—SO₂ Thiophenyl Z₁: F (3) S pyridinyl NH—SO₂ Thiophenyl Z₁: F (2) Z₂:F (3) S Pyridinyl NH—SO₂ Thiophenyl Z₁: Cl (2) S Pyridinyl NH—SO₂Thiophenyl Z₁: Cl (3) S Pyridinyl NH—SO₂ Thiophenyl Z₁: Cl (2) Z₂: Cl(3) S Pyridinyl NH—SO₂ Thiophenyl Z₁: F (2) Z₂: Cl (3) S PyridinylNH—SO₂ Thiophenyl Z₁: Cl (2) Z₂: F (3) S Pyridinyl NH—SO₂ Thiophenyl Z₁:CH₃ (2) S Pyridinyl NH—SO₂ Thiophenyl Z₁: CH₃ (3) S Pyridinyl NH—SO₂Thiophenyl Z₁: CH₂—CH₃ (2) S Pyridinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₃ (3)S Pyridinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (2) S PyridinylNH—SO₂ Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (3) S Pyridinyl NH—SO₂Thiophenyl Z₁: CH₂F (2) S Pyridinyl NH—SO₂ Thiophenyl Z₁: CH₂F (3) SPyridinyl NH—SO₂ Thiophenyl Z₁: CHF₂ (2) S Pyridinyl NH—SO₂ ThiophenylZ₁: CHF₂ (3) S Pyridinyl NH—SO₂ Thiophenyl Z₁: CF₃ (2) S PyridinylNH—SO₂ Thiophenyl Z₁: CF₃ (3) S Pyridinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₂F(2) S Pyridinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₂F (3) S Pyridinyl NH—SO₂Thiophenyl Z₁: CH₂—CHF₂ (2) S Pyridinyl NH—SO₂ Thiophenyl Z₁: CH₂—CHF₂(3) S Pyridinyl NH—SO₂ Thiophenyl Z₁: CH₂—CF₃ (2) S Pyridinyl NH—SO₂Thiophenyl Z₁: CH₂—CF₃ (3) S pyridinyl NH—SO₂ Thiazolyl None S pyridinylNH—SO₂ Thiazolyl Z₁: F (2) S pyridinyl NH—SO₂ Thiazolyl Z₁: F (3) Spyridinyl NH—SO₂ Thiazolyl Z₁: F (2) Z₂: F (3) S Pyridinyl NH—SO₂Thiazolyl Z₁: Cl (2) S Pyridinyl NH—SO₂ Thiazolyl Z₁: Cl (3) S PyridinylNH—SO₂ Thiazolyl Z₁: Cl (2) Z₂: Cl (3) S Pyridinyl NH—SO₂ Thiazolyl Z₁:F (2) Z₂: Cl (3) S Pyridinyl NH—SO₂ Thiazolyl Z₁: Cl (2) Z₂: F (3) SPyridinyl NH—SO₂ Thiazolyl Z₁: CH₃ (2) S Pyridinyl NH—SO₂ Thiazolyl Z₁:CH₃ (3) S Pyridinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₃ (2) S Pyridinyl NH—SO₂Thiazolyl Z₁: CH₂—CH₃ (3) S Pyridinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₂—CH₃or iPr (2) S Pyridinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) SPyridinyl NH—SO₂ Thiazolyl Z₁: CH₂F (2) S Pyridinyl NH—SO₂ Thiazolyl Z₁:CH₂F (3) S Pyridinyl NH—SO₂ Thiazolyl Z₁: CHF₂ (2) S Pyridinyl NH—SO₂Thiazolyl Z₁: CHF₂ (3) S Pyridinyl NH—SO₂ Thiazolyl Z₁: CF₃ (2) SPyridinyl NH—SO₂ Thiazolyl Z₁: CF₃ (3) S Pyridinyl NH—SO₂ Thiazolyl Z₁:CH₂—CH₂F (2) S Pyridinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₂F (3) S PyridinylNH—SO₂ Thiazolyl Z₁: CH₂—CHF₂ (2) S Pyridinyl NH—SO₂ Thiazolyl Z₁:CH₂—CHF₂ (3) S Pyridinyl NH—SO₂ Thiazolyl Z₁: CH₂—CF₃ (2) S PyridinylNH—SO₂ Thiazolyl Z₁: CH₂—CF₃ (3) S Pyrimidinyl NH—CH₂ Phenyl None SPyrimidinyl NH—CH₂ Phenyl Z₁: F (para) S Pyrimidinyl NH—CH₂ phenyl Z₁: F(meta) S Pyrimidinyl NH—CH₂ phenyl Z₁: F (ortho) S Pyrimidinyl NH—CH₂phenyl Z₁: F (para) Z₂: F (meta) S Pyrimidinyl NH—CH₂ Phenyl Z₁: Cl(meta) S Pyrimidinyl NH—CH₂ Phenyl Z₁: Cl (para) S Pyrimidinyl NH—CH₂Phenyl Z₁: Cl (para) Z₂: Cl (meta) S Pyrimidinyl NH—CH₂ Phenyl Z₁: F(para) Z₂: Cl (meta) S Pyrimidinyl NH—CH₂ Phenyl Z₁: Cl (para) Z₂: F(meta) S Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₃ (para) S Pyrimidinyl NH—CH₂Phenyl Z₁: CH₃ (meta) S Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₃ (ortho) SPyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CH₃ (para) S Pyrimidinyl NH—CH₂ PhenylZ₁: CH₂—CH₃ (meta) S Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CH₃ (ortho) SPyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (para) S PyrimidinylNH—CH₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) S Pyrimidinyl NH—CH₂ PhenylZ₁: CH₂—CH₂—CH₃ or iPr (ortho) S Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂F(para) S Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂F (meta) S Pyrimidinyl NH—CH₂Phenyl Z₁: CH₂F (ortho) S Pyrimidinyl NH—CH₂ Phenyl Z₁: CHF₂ (para) SPyrimidinyl NH—CH₂ Phenyl Z₁: CHF₂ (meta) S Pyrimidinyl NH—CH₂ PhenylZ₁: CHF₂ (ortho) S Pyrimidinyl NH—CH₂ Phenyl Z₁: CF₃ (para) SPyrimidinyl NH—CH₂ Phenyl Z₁: CF₃ (meta) S Pyrimidinyl NH—CH₂ Phenyl Z₁:CF₃ (ortho) S Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂F (para) SPyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂F (meta) S Pyrimidinyl NH—CH₂Phenyl Z₁: CH₂—CH₂F (ortho) S Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CHF₂(para) S Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CHF₂ (meta) S PyrimidinylNH—CH₂ Phenyl Z₁: CH₂—CHF₂ (ortho) S Pyrimidinyl NH—CH₂ Phenyl Z₁:CH₂—CF₃ (para) S Pyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CF₃ (meta) SPyrimidinyl NH—CH₂ Phenyl Z₁: CH₂—CF₃ (ortho) S Pyrimidinyl NH—CH₂Pyridinyl None S Pyrimidinyl NH—CH₂ Pyridinyl Z₁: F (para) S PyrimidinylNH—CH₂ Pyridinyl Z₁: F (meta) S Pyrimidinyl NH—CH₂ Pyridinyl Z₁: F(ortho) S Pyrimidinyl NH—CH₂ Pyridinyl Z₁: F (para) Z₂: F (meta) SPyrimidinyl NH—CH₂ Pyridinyl Z₁: Cl (meta) S Pyrimidinyl NH—CH₂Pyridinyl Z₁: Cl (para) S Pyrimidinyl NH—CH₂ Pyridinyl Z₁: Cl (para) Z₂:Cl (meta) S Pyrimidinyl NH—CH₂ Pyridinyl Z₁: F (para) Z₂: Cl (meta) SPyrimidinyl NH—CH₂ Pyridinyl Z₁: Cl (para) Z₂: F (meta) S PyrimidinylNH—CH₂ Pyridinyl Z₁: CH₃ (para) S Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₃(meta) S Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₃ (ortho) S PyrimidinylNH—CH₂ Pyridinyl Z₁: CH₂—CH₃ (para) S Pyrimidinyl NH—CH₂ Pyridinyl Z₁:CH₂—CH₃ (meta) S Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₃ (ortho) SPyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) S PyrimidinylNH—CH₂ Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) S Pyrimidinyl NH—CH₂Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) S Pyrimidinyl NH—CH₂ PyridinylZ₁: CH₂F (para) S Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₂F (meta) SPyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₂F (ortho) S Pyrimidinyl NH—CH₂Pyridinyl Z₁: CHF₂ (para) S Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CHF₂ (meta)S Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CHF₂ (ortho) S Pyrimidinyl NH—CH₂Pyridinyl Z₁: CF₃ (para) S Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CF₃ (meta) SPyrimidinyl NH—CH₂ Pyridinyl Z₁: CF₃ (ortho) S Pyrimidinyl NH—CH₂Pyridinyl Z₁: CH₂—CH₂F (para) S Pyrimidinyl NH—CH₂ Pyridinyl Z₁:CH₂—CH₂F (meta) S Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₂F (ortho) SPyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₂—CHF₂ (para) S Pyrimidinyl NH—CH₂Pyridinyl Z₁: CH₂—CHF₂ (meta) S Pyrimidinyl NH—CH₂ Pyridinyl Z₁:CH₂—CHF₂ (ortho) S Pyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₂—CF₃ (para) SPyrimidinyl NH—CH₂ Pyridinyl Z₁: CH₂—CF₃ (meta) S Pyrimidinyl NH—CH₂Pyridinyl Z₁: CH₂—CF₃ (ortho) S Pyrimidinyl NH—CH₂ Pyrimidinyl None SPyrimidinyl NH—CH₂ Pyrimidinyl Z₁: F (para) S Pyrimidinyl NH—CH₂Pyrimidinyl Z₁: F (meta) S Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: F (ortho)S Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: F (para) Z₂: F (meta) S PyrimidinylNH—CH₂ Pyrimidinyl Z₁: Cl (meta) S Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: Cl(para) S Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: Cl (para) Z₂: Cl (meta) SPyrimidinyl NH—CH₂ Pyrimidinyl Z₁: F (para) Z₂: Cl (meta) S PyrimidinylNH—CH₂ Pyrimidinyl Z₁: Cl (para) Z₂: F (meta) S Pyrimidinyl NH—CH₂Pyrimidinyl Z₁: CH₃ (para) S Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₃(meta) S Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₃ (ortho) S PyrimidinylNH—CH₂ Pyrimidinyl Z₁: CH₂—CH₃ (para) S Pyrimidinyl NH—CH₂ PyrimidinylZ₁: CH₂—CH₃ (meta) S Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₃ (ortho)S Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) SPyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) SPyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) SPyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₂F (para) S Pyrimidinyl NH—CH₂Pyrimidinyl Z₁: CH₂F (meta) S Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₂F(ortho) S Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CHF₂ (para) S PyrimidinylNH—CH₂ Pyrimidinyl Z₁: CHF₂ (meta) S Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁:CHF₂ (ortho) S Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CF₃ (para) SPyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CF₃ (meta) S Pyrimidinyl NH—CH₂Pyrimidinyl Z₁: CF₃ (ortho) S Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁:CH₂—CH₂F (para) S Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₂F (meta) SPyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₂F (ortho) S Pyrimidinyl NH—CH₂Pyrimidinyl Z₁: CH₂—CHF₂ (para) S Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁:CH₂—CHF₂ (meta) S Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CHF₂ (ortho) SPyrimidinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CF₃ (para) S Pyrimidinyl NH—CH₂Pyrimidinyl Z₁: CH₂—CF₃ (meta) S Pyrimidinyl NH—CH₂ Pyrimidinyl Z₁:CH₂—CF₃ (ortho) S Pyrimidinyl NH—CH₂ Pyrazinyl None S Pyrimidinyl NH—CH₂Pyrazinyl Z₁: F (para) S Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: F (meta) SPyrimidinyl NH—CH₂ Pyrazinyl Z₁: F (ortho) S Pyrimidinyl NH—CH₂Pyrazinyl Z₁: F (para) Z₂: F (meta) S Pyrimidinyl NH—CH₂ Pyrazinyl Z₁:Cl (meta) S Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: Cl (para) S PyrimidinylNH—CH₂ Pyrazinyl Z₁: Cl (para) Z₂: Cl (meta) S Pyrimidinyl NH—CH₂Pyrazinyl Z₁: F (para) Z₂: Cl (meta) S Pyrimidinyl NH—CH₂ Pyrazinyl Z₁:Cl (para) Z₂: F (meta) S Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₃ (para) SPyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₃ (meta) S Pyrimidinyl NH—CH₂Pyrazinyl Z₁: CH₃ (ortho) S Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₃(para) S Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₃ (meta) S PyrimidinylNH—CH₂ Pyrazinyl Z₁: CH₂—CH₃ (ortho) S Pyrimidinyl NH—CH₂ Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (para) S Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₂—CH₃or iPr (meta) S Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr(ortho) S Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₂F (para) S PyrimidinylNH—CH₂ Pyrazinyl Z₁: CH₂F (meta) S Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₂F(ortho) S Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CHF₂ (para) S PyrimidinylNH—CH₂ Pyrazinyl Z₁: CHF₂ (meta) S Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CHF₂(ortho) S Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CF₃ (para) S PyrimidinylNH—CH₂ Pyrazinyl Z₁: CF₃ (meta) S Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CF₃(ortho) S Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₂F (para) S PyrimidinylNH—CH₂ Pyrazinyl Z₁: CH₂—CH₂F (meta) S Pyrimidinyl NH—CH₂ Pyrazinyl Z₁:CH₂—CH₂F (ortho) S Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CHF₂ (para) SPyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CHF₂ (meta) S Pyrimidinyl NH—CH₂Pyrazinyl Z₁: CH₂—CHF₂ (ortho) S Pyrimidinyl NH—CH₂ Pyrazinyl Z₁:CH₂—CF₃ (para) S Pyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CF₃ (meta) SPyrimidinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CF₃ (ortho) S Pyrimidinyl NH—CH₂Pyrrolyl None S Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: F (2) S PyrimidinylNH—CH₂ Pyrrolyl Z₁: F (3) S Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: F (2) Z₂: F(3) S Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: Cl (2) S Pyrimidinyl NH—CH₂Pyrrolyl Z₁: Cl (3) S Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: Cl (2) Z₂: Cl (3)S Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: F (2) Z₂: Cl (3) S Pyrimidinyl NH—CH₂Pyrrolyl Z₁: Cl (2) Z₂: F (3) S Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: CH₃ (2)S Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: CH₃ (3) S Pyrimidinyl NH—CH₂ PyrrolylZ₁: CH₂—CH₃ (2) S Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₃ (3) SPyrimidinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) S PyrimidinylNH—CH₂ Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) S Pyrimidinyl NH—CH₂ PyrrolylZ₁: CH₂F (2) S Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: CH₂F (3) S PyrimidinylNH—CH₂ Pyrrolyl Z₁: CHF₂ (2) S Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: CHF₂ (3)S Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: CF₃ (2) S Pyrimidinyl NH—CH₂ PyrrolylZ₁: CF₃ (3) S Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₂F (2) S PyrimidinylNH—CH₂ Pyrrolyl Z₁: CH₂—CH₂F (3) S Pyrimidinyl NH—CH₂ Pyrrolyl Z₁:CH₂—CHF₂ (2) S Pyrimidinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CHF₂ (3) SPyrimidinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CF₃ (2) S Pyrimidinyl NH—CH₂Pyrrolyl Z₁: CH₂—CF₃ (3) S Pyrimidinyl NH—CH₂ Imidazolyl None SPyrimidinyl NH—CH₂ Imidazolyl Z₁: F (2) S Pyrimidinyl NH—CH₂ ImidazolylZ₁: F (3) S Pyrimidinyl NH—CH₂ Imidazolyl Z₁: F (2) Z₂: F (3) SPyrimidinyl NH—CH₂ Imidazolyl Z₁: Cl (2) S Pyrimidinyl NH—CH₂ ImidazolylZ₁: Cl (3) S Pyrimidinyl NH—CH₂ Imidazolyl Z₁: Cl (2) Z₂: Cl (3) SPyrimidinyl NH—CH₂ Imidazolyl Z₁: F (2) Z₂: Cl (3) S Pyrimidinyl NH—CH₂Imidazolyl Z₁: Cl (2) Z₂: F (3) S Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CH₃(2) S Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CH₃ (3) S Pyrimidinyl NH—CH₂Imidazolyl Z₁: CH₂—CH₃ (2) S Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₃(3) S Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) SPyrimidinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) S PyrimidinylNH—CH₂ Imidazolyl Z₁: CH₂F (2) S Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CH₂F(3) S Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CHF₂ (2) S Pyrimidinyl NH—CH₂Imidazolyl Z₁: CHF₂ (3) S Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CF₃ (2) SPyrimidinyl NH—CH₂ Imidazolyl Z₁: CF₃ (3) S Pyrimidinyl NH—CH₂Imidazolyl Z₁: CH₂—CH₂F (2) S Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₂F(3) S Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CH₂—CHF₂ (2) S PyrimidinylNH—CH₂ Imidazolyl Z₁: CH₂—CHF₂ (3) S Pyrimidinyl NH—CH₂ Imidazolyl Z₁:CH₂—CF₃ (2) S Pyrimidinyl NH—CH₂ Imidazolyl Z₁: CH₂—CF₃ (3) SPyrimidinyl NH—CH₂ Furanyl None S Pyrimidinyl NH—CH₂ Furanyl Z₁: F (2) SPyrimidinyl NH—CH₂ Furanyl Z₁: F (3) S Pyrimidinyl NH—CH₂ Furanyl Z₁: F(2) Z₂: F (3) S Pyrimidinyl NH—CH₂ Furanyl Z₁: Cl (2) S PyrimidinylNH—CH₂ Furanyl Z₁: Cl (3) S Pyrimidinyl NH—CH₂ Furanyl Z₁: Cl (2) Z₂: Cl(3) S Pyrimidinyl NH—CH₂ Furanyl Z₁: F (2) Z₂: Cl (3) S PyrimidinylNH—CH₂ Furanyl Z₁: Cl (2) Z₂: F (3) S Pyrimidinyl NH—CH₂ Furanyl Z₁: CH₃(2) S Pyrimidinyl NH—CH₂ Furanyl Z₁: CH₃ (3) S Pyrimidinyl NH—CH₂Furanyl Z₁: CH₂—CH₃ (2) S Pyrimidinyl NH—CH₂ Furanyl Z₁: CH₂—CH₃ (3) SPyrimidinyl NH—CH₂ Furanyl Z₁: CH₂—CH₂—CH₃ or iPr (2) S PyrimidinylNH—CH₂ Furanyl Z₁: CH₂—CH₂—CH₃ or iPr (3) S Pyrimidinyl NH—CH₂ FuranylZ₁: CH₂F (2) S Pyrimidinyl NH—CH₂ Furanyl Z₁: CH₂F (3) S PyrimidinylNH—CH₂ Furanyl Z₁: CHF₂ (2) S Pyrimidinyl NH—CH₂ Furanyl Z₁: CHF₂ (3) SPyrimidinyl NH—CH₂ Furanyl Z₁: CF₃ (2) S Pyrimidinyl NH—CH₂ Furanyl Z₁:CF₃ (3) S Pyrimidinyl NH—CH₂ Furanyl Z₁: CH₂—CH₂F (2) S PyrimidinylNH—CH₂ Furanyl Z₁: CH₂—CH₂F (3) S Pyrimidinyl NH—CH₂ Furanyl Z₁:CH₂—CHF₂ (2) S Pyrimidinyl NH—CH₂ Furanyl Z₁: CH₂—CHF₂ (3) S PyrimidinylNH—CH₂ Furanyl Z₁: CH₂—CF₃ (2) S Pyrimidinyl NH—CH₂ Furanyl Z₁: CH₂—CF₃(3) S Pyrimidinyl NH—CH₂ Oxazolyl None S Pyrimidinyl NH—CH₂ Oxazolyl Z₁:F (2) S Pyrimidinyl NH—CH₂ Oxazolyl Z₁: F (3) S Pyrimidinyl NH—CH₂Oxazolyl Z₁: F (2) Z₂: F (3) S Pyrimidinyl NH—CH₂ Oxazolyl Z₁: Cl (2) SPyrimidinyl NH—CH₂ Oxazolyl Z₁: Cl (3) S Pyrimidinyl NH—CH₂ Oxazolyl Z₁:Cl (2) Z₂: Cl (3) S Pyrimidinyl NH—CH₂ Oxazolyl Z₁: F (2) Z₂: Cl (3) SPyrimidinyl NH—CH₂ Oxazolyl Z₁: Cl (2) Z₂: F (3) S Pyrimidinyl NH—CH₂Oxazolyl Z₁: CH₃ (2) S Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CH₃ (3) SPyrimidinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₃ (2) S Pyrimidinyl NH—CH₂Oxazolyl Z₁: CH₂—CH₃ (3) S Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₂—CH₃or iPr (2) S Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) SPyrimidinyl NH—CH₂ Oxazolyl Z₁: CH₂F (2) S Pyrimidinyl NH—CH₂ OxazolylZ₁: CH₂F (3) S Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CHF₂ (2) S PyrimidinylNH—CH₂ Oxazolyl Z₁: CHF₂ (3) S Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CF₃ (2) SPyrimidinyl NH—CH₂ Oxazolyl Z₁: CF₃ (3) S Pyrimidinyl NH—CH₂ OxazolylZ₁: CH₂—CH₂F (2) S Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₂F (3) SPyrimidinyl NH—CH₂ Oxazolyl Z₁: CH₂—CHF₂ (2) S Pyrimidinyl NH—CH₂Oxazolyl Z₁: CH₂—CHF₂ (3) S Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CH₂—CF₃ (2)S Pyrimidinyl NH—CH₂ Oxazolyl Z₁: CH₂—CF₃ (3) S Pyrimidinyl NH—CH₂Thiophenyl None S Pyrimidinyl NH—CH₂ Thiophenyl Z₁: F (2) S PyrimidinylNH—CH₂ Thiophenyl Z₁: F (3) S Pyrimidinyl NH—CH₂ Thiophenyl Z₁: F (2)Z₂: F (3) S Pyrimidinyl NH—CH₂ Thiophenyl Z₁: Cl (2) S PyrimidinylNH—CH₂ Thiophenyl Z₁: Cl (3) S Pyrimidinyl NH—CH₂ Thiophenyl Z₁: Cl (2)Z₂: Cl (3) S Pyrimidinyl NH—CH₂ Thiophenyl Z₁: F (2) Z₂: Cl (3) SPyrimidinyl NH—CH₂ Thiophenyl Z₁: Cl (2) Z₂: F (3) S Pyrimidinyl NH—CH₂Thiophenyl Z₁: CH₃ (2) S Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CH₃ (3) SPyrimidinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₃ (2) S Pyrimidinyl NH—CH₂Thiophenyl Z₁: CH₂—CH₃ (3) S Pyrimidinyl NH—CH₂ Thiophenyl Z₁:CH₂—CH₂—CH₃ or iPr (2) S Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₂—CH₃or iPr (3) S Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CH₂F (2) S PyrimidinylNH—CH₂ Thiophenyl Z₁: CH₂F (3) S Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CHF₂(2) S Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CHF₂ (3) S Pyrimidinyl NH—CH₂Thiophenyl Z₁: CF₃ (2) S Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CF₃ (3) SPyrimidinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₂F (2) S Pyrimidinyl NH—CH₂Thiophenyl Z₁: CH₂—CH₂F (3) S Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CH₂—CHF₂(2) S Pyrimidinyl NH—CH₂ Thiophenyl Z₁: CH₂—CHF₂ (3) S PyrimidinylNH—CH₂ Thiophenyl Z₁: CH₂—CF₃ (2) S Pyrimidinyl NH—CH₂ Thiophenyl Z₁:CH₂—CF₃ (3) S Pyrimidinyl NH—CH₂ Thiazolyl None S Pyrimidinyl NH—CH₂Thiazolyl Z₁: F (2) S Pyrimidinyl NH—CH₂ Thiazolyl Z₁: F (3) SPyrimidinyl NH—CH₂ Thiazolyl Z₁: F (2) Z₂: F (3) S Pyrimidinyl NH—CH₂Thiazolyl Z₁: Cl (2) S Pyrimidinyl NH—CH₂ Thiazolyl Z₁: Cl (3) SPyrimidinyl NH—CH₂ Thiazolyl Z₁: Cl (2) Z₂: Cl (3) S Pyrimidinyl NH—CH₂Thiazolyl Z₁: F (2) Z₂: Cl (3) S Pyrimidinyl NH—CH₂ Thiazolyl Z₁: Cl (2)Z₂: F (3) S Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CH₃ (2) S PyrimidinylNH—CH₂ Thiazolyl Z₁: CH₃ (3) S Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₃(2) S Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₃ (3) S Pyrimidinyl NH—CH₂Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) S Pyrimidinyl NH—CH₂ Thiazolyl Z₁:CH₂—CH₂—CH₃ or iPr (3) S Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CH₂F (2) SPyrimidinyl NH—CH₂ Thiazolyl Z₁: CH₂F (3) S Pyrimidinyl NH—CH₂ ThiazolylZ₁: CHF₂ (2) S Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CHF₂ (3) S PyrimidinylNH—CH₂ Thiazolyl Z₁: CF₃ (2) S Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CF₃ (3)S Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₂F (2) S Pyrimidinyl NH—CH₂Thiazolyl Z₁: CH₂—CH₂F (3) S Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CH₂CHF₂(2) S Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CH₂CHF₂ (3) S Pyrimidinyl NH—CH₂Thiazolyl Z₁: CH₂—CF₃ (2) S Pyrimidinyl NH—CH₂ Thiazolyl Z₁: CH₂—CF₃ (3)S Pyrimidinyl NH—C(O) Phenyl None S Pyrimidinyl NH—C(O) Phenyl Z₁: F(para) S Pyrimidinyl NH—C(O) phenyl Z₁: F (meta) S Pyrimidinyl NH—C(O)phenyl Z₁: F (ortho) S Pyrimidinyl NH—C(O) phenyl Z₁: F (para) Z₂: F(meta) S Pyrimidinyl NH—C(O) Phenyl Z₁: Cl (meta) S Pyrimidinyl NH—C(O)Phenyl Z₁: Cl (para) S Pyrimidinyl NH—C(O) Phenyl Z₁: Cl (para) Z₂: Cl(meta) S Pyrimidinyl NH—C(O) Phenyl Z₁: F (para) Z₂: Cl (meta) SPyrimidinyl NH—C(O) Phenyl Z₁: Cl (para) Z₂: F (meta) S PyrimidinylNH—C(O) Phenyl Z₁: CH₃ (para) S Pyrimidinyl NH—C(O) Phenyl Z₁: CH₃(meta) S Pyrimidinyl NH—C(O) Phenyl Z₁: CH₃ (ortho) S PyrimidinylNH—C(O) Phenyl Z₁: CH₂—CH₃ (para) S Pyrimidinyl NH—C(O) Phenyl Z₁:CH₂—CH₃ (meta) S Pyrimidinyl NH—C(O) Phenyl Z₁: CH₂—CH₃ (ortho) SPyrimidinyl NH—C(O) Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (para) S PyrimidinylNH—C(O) Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) S Pyrimidinyl NH—C(O)Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) S Pyrimidinyl NH—C(O) Phenyl Z₁:CH₂F (para) S Pyrimidinyl NH—C(O) Phenyl Z₁: CH₂F (meta) S PyrimidinylNH—C(O) Phenyl Z₁: CH₂F (ortho) S Pyrimidinyl NH—C(O) Phenyl Z₁: CHF₂(para) S Pyrimidinyl NH—C(O) Phenyl Z₁: CHF₂ (meta) S PyrimidinylNH—C(O) Phenyl Z₁: CHF₂ (ortho) S Pyrimidinyl NH—C(O) Phenyl Z₁: CF₃(para) S Pyrimidinyl NH—C(O) Phenyl Z₁: CF₃ (meta) S Pyrimidinyl NH—C(O)Phenyl Z₁: CF₃ (ortho) S Pyrimidinyl NH—C(O) Phenyl Z₁: CH₂—CH₂F (para)S Pyrimidinyl NH—C(O) Phenyl Z₁: CH₂—CH₂F (meta) S Pyrimidinyl NH—C(O)Phenyl Z₁: CH₂—CH₂F (ortho) S Pyrimidinyl NH—C(O) Phenyl Z₁: CH₂—CHF₂(para) S Pyrimidinyl NH—C(O) Phenyl Z₁: CH₂—CHF₂ (meta) S PyrimidinylNH—C(O) Phenyl Z₁: CH₂—CHF₂ (ortho) S Pyrimidinyl NH—C(O) Phenyl Z₁:CH₂—CF₃ (para) S Pyrimidinyl NH—C(O) Phenyl Z₁: CH₂—CF₃ (meta) SPyrimidinyl NH—C(O) Phenyl Z₁: CH₂—CF₃ (ortho) S Pyrimidinyl NH—C(O)Pyridinyl None S Pyrimidinyl NH—C(O) Pyridinyl Z₁: F (para) SPyrimidinyl NH—C(O) Pyridinyl Z₁: F (meta) S Pyrimidinyl NH—C(O)Pyridinyl Z₁: F (ortho) S Pyrimidinyl NH—C(O) Pyridinyl Z₁: F (para) Z₂:F (meta) S Pyrimidinyl NH—C(O) Pyridinyl Z₁: Cl (meta) S PyrimidinylNH—C(O) Pyridinyl Z₁: Cl (para) S Pyrimidinyl NH—C(O) Pyridinyl Z₁: Cl(para) Z₂: Cl (meta) S Pyrimidinyl NH—C(O) Pyridinyl Z₁: F (para) Z₂: Cl(meta) S Pyrimidinyl NH—C(O) Pyridinyl Z₁: Cl (para) Z₂: F (meta) SPyrimidinyl NH—C(O) Pyridinyl Z₁: CH₃ (para) S Pyrimidinyl NH—C(O)Pyridinyl Z₁: CH₃ (meta) S Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₃ (ortho)S Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₃ (para) S Pyrimidinyl NH—C(O)Pyridinyl Z₁: CH₂—CH₃ (meta) S Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₃(ortho) S Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) SPyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) SPyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) SPyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂F (para) S Pyrimidinyl NH—C(O)Pyridinyl Z₁: CH₂F (meta) S Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂F(ortho) S Pyrimidinyl NH—C(O) Pyridinyl Z₁: CHF₂ (para) S PyrimidinylNH—C(O) Pyridinyl Z₁: CHF₂ (meta) S Pyrimidinyl NH—C(O) Pyridinyl Z₁:CHF₂ (ortho) S Pyrimidinyl NH—C(O) Pyridinyl Z₁: CF₃ (para) SPyrimidinyl NH—C(O) Pyridinyl Z₁: CF₃ (meta) S Pyrimidinyl NH—C(O)Pyridinyl Z₁: CF₃ (ortho) S Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₂F(para) S Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₂F (meta) S PyrimidinylNH—C(O) Pyridinyl Z₁: CH₂—CH₂F (ortho) S Pyrimidinyl NH—C(O) PyridinylZ₁: CH₂—CHF₂ (para) S Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂—CHF₂ (meta)S Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂—CHF₂ (ortho) S PyrimidinylNH—C(O) Pyridinyl Z₁: CH₂—CF₃ (para) S Pyrimidinyl NH—C(O) Pyridinyl Z₁:CH₂—CF₃ (meta) S Pyrimidinyl NH—C(O) Pyridinyl Z₁: CH₂—CF₃ (ortho) SPyrimidinyl NH—C(O) Pyrimidinyl None S Pyrimidinyl NH—C(O) PyrimidinylZ₁: F (para) S Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: F (meta) SPyrimidinyl NH—C(O) Pyrimidinyl Z₁: F (ortho) S Pyrimidinyl NH—C(O)Pyrimidinyl Z₁: F (para) Z₂: F (meta) S Pyrimidinyl NH—C(O) PyrimidinylZ₁: Cl (meta) S Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: Cl (para) SPyrimidinyl NH—C(O) Pyrimidinyl Z₁: Cl (para) Z₂: Cl (meta) SPyrimidinyl NH—C(O) Pyrimidinyl Z₁: F (para) Z₂: Cl (meta) S PyrimidinylNH—C(O) Pyrimidinyl Z₁: Cl (para) Z₂: F (meta) S Pyrimidinyl NH—C(O)Pyrimidinyl Z₁: CH₃ (para) S Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₃(meta) S Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₃ (ortho) S PyrimidinylNH—C(O) Pyrimidinyl Z₁: CH₂—CH₃ (para) S Pyrimidinyl NH—C(O) PyrimidinylZ₁: CH₂—CH₃ (meta) S Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CH₃ (ortho)S Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) SPyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) SPyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) SPyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₂F (para) S Pyrimidinyl NH—C(O)Pyrimidinyl Z₁: CH₂F (meta) S Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₂F(ortho) S Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CHF₂ (para) S PyrimidinylNH—C(O) Pyrimidinyl Z₁: CHF₂ (meta) S Pyrimidinyl NH—C(O) PyrimidinylZ₁: CHF₂ (ortho) S Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CF₃ (para) SPyrimidinyl NH—C(O) Pyrimidinyl Z₁: CF₃ (meta) S Pyrimidinyl NH—C(O)Pyrimidinyl Z₁: CF₃ (ortho) S Pyrimidinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CH₂F (para) S Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CH₂F (meta) SPyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CH₂F (ortho) S PyrimidinylNH—C(O) Pyrimidinyl Z₁: CH₂—CHF₂ (para) S Pyrimidinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CHF₂ (meta) S Pyrimidinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CHF₂ (ortho) S Pyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CF₃ (para) SPyrimidinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CF₃ (meta) S Pyrimidinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CF₃ (ortho) S Pyrimidinyl NH—C(O) Pyrazinyl None SPyrimidinyl NH—C(O) Pyrazinyl Z₁: F (para) S Pyrimidinyl NH—C(O)Pyrazinyl Z₁: F (meta) S Pyrimidinyl NH—C(O) Pyrazinyl Z₁: F (ortho) SPyrimidinyl NH—C(O) Pyrazinyl Z₁: F (para) Z₂: F (meta) S PyrimidinylNH—C(O) Pyrazinyl Z₁: Cl (meta) S Pyrimidinyl NH—C(O) Pyrazinyl Z₁: Cl(para) S Pyrimidinyl NH—C(O) Pyrazinyl Z₁: Cl (para) Z₂: Cl (meta) SPyrimidinyl NH—C(O) Pyrazinyl Z₁: F (para) Z₂: Cl (meta) S PyrimidinylNH—C(O) Pyrazinyl Z₁: Cl (para) Z₂: F (meta) S Pyrimidinyl NH—C(O)Pyrazinyl Z₁: CH₃ (para) S Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₃ (meta)S Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₃ (ortho) S Pyrimidinyl NH—C(O)Pyrazinyl Z₁: CH₂—CH₃ (para) S Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₂—CH₃(meta) S Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₂—CH₃ (ortho) S PyrimidinylNH—C(O) Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) S Pyrimidinyl NH—C(O)Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) S Pyrimidinyl NH—C(O) PyrazinylZ₁: CH₂—CH₂—CH₃ or iPr (ortho) S Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₂F(para) S Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₂F (meta) S PyrimidinylNH—C(O) Pyrazinyl Z₁: CH₂F (ortho) S Pyrimidinyl NH—C(O) Pyrazinyl Z₁:CHF₂ (para) S Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CHF₂ (meta) SPyrimidinyl NH—C(O) Pyrazinyl Z₁: CHF₂ (ortho) S Pyrimidinyl NH—C(O)Pyrazinyl Z₁: CF₃ (para) S Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CF₃ (meta)S Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CF₃ (ortho) S Pyrimidinyl NH—C(O)Pyrazinyl Z₁: CH₂—CH₂F (para) S Pyrimidinyl NH—C(O) Pyrazinyl Z₁:CH₂—CH₂F (meta) S Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₂—CH₂F (ortho) SPyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₂—CHF₂ (para) S Pyrimidinyl NH—C(O)Pyrazinyl Z₁: CH₂—CHF₂ (meta) S Pyrimidinyl NH—C(O) Pyrazinyl Z₁:CH₂—CHF₂ (ortho) S Pyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₂—CF₃ (para) SPyrimidinyl NH—C(O) Pyrazinyl Z₁: CH₂—CF₃ (meta) S Pyrimidinyl NH—C(O)Pyrazinyl Z₁: CH₂—CF₃ (ortho) S Pyrimidinyl NH—C(O) Pyrrolyl None SPyrimidinyl NH—C(O) Pyrrolyl Z₁: F (2) S Pyrimidinyl NH—C(O) PyrrolylZ₁: F (3) S Pyrimidinyl NH—C(O) Pyrrolyl Z₁: F (2) Z₂: F (3) SPyrimidinyl NH—C(O) Pyrrolyl Z₁: Cl (2) S Pyrimidinyl NH—C(O) PyrrolylZ₁: Cl (3) S Pyrimidinyl NH—C(O) Pyrrolyl Z₁: Cl (2) Z₂: Cl (3) SPyrimidinyl NH—C(O) Pyrrolyl Z₁: F (2) Z₂: Cl (3) S Pyrimidinyl NH—C(O)Pyrrolyl Z₁: Cl (2) Z₁: F (3) S Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CH₃ (2)S Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CH₃ (3) S Pyrimidinyl NH—C(O)Pyrrolyl Z₁: CH₂—CH₃ (2) S Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₃ (3)S Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) S PyrimidinylNH—C(O) Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) S Pyrimidinyl NH—C(O)Pyrrolyl Z₁: CH₂F (2) S Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CH₂F (3) SPyrimidinyl NH—C(O) Pyrrolyl Z₁: CHF₂ (2) S Pyrimidinyl NH—C(O) PyrrolylZ₁: CHF₂ (3) S Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CF₃ (2) S PyrimidinylNH—C(O) Pyrrolyl Z₁: CF₃ (3) S Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₂F(2) S Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₂F (3) S PyrimidinylNH—C(O) Pyrrolyl Z₁: CH₂—CHF₂ (2) S Pyrimidinyl NH—C(O) Pyrrolyl Z₁:CH₂—CHF₂ (3) S Pyrimidinyl NH—C(O) Pyrrolyl Z₁: CH₂—CF₃ (2) SPyrimidinyl NH—C(O) Pyrrolyl Z₁: CH₂—CF₃ (3) S Pyrimidinyl NH—C(O)Imidazolyl None S Pyrimidinyl NH—C(O) Imidazolyl Z₁: F (2) S PyrimidinylNH—C(O) Imidazolyl Z₁: F (3) S Pyrimidinyl NH—C(O) Imidazolyl Z₁: F (2)Z₂: F (3) S Pyrimidinyl NH—C(O) Imidazolyl Z₁: Cl (2) S PyrimidinylNH—C(O) Imidazolyl Z₁: Cl (3) S Pyrimidinyl NH—C(O) Imidazolyl Z₁: Cl(2) Z₂: Cl (3) S Pyrimidinyl NH—C(O) Imidazolyl Z₁: F (2) Z₂: Cl (3) SPyrimidinyl NH—C(O) Imidazolyl Z₁: Cl (2) Z₂: F (3) S PyrimidinylNH—C(O) Imidazolyl Z₁: CH₃ (2) S Pyrimidinyl NH—C(O) Imidazolyl Z₁: CH₃(3) S Pyrimidinyl NH—C(O) Imidazolyl Z₁: CH₂—CH₃ (2) S PyrimidinylNH—C(O) Imidazolyl Z₁: CH₂—CH₃ (3) S Pyrimidinyl NH—C(O) Imidazolyl Z₁:CH₂—CH₂—CH₃ or iPr (2) S Pyrimidinyl NH—C(O) Imidazolyl Z₁: CH₂—CH₂—CH₃or iPr (3) S Pyrimidinyl NH—C(O) Imidazolyl Z₁: CH₂F (2) S PyrimidinylNH—C(O) Imidazolyl Z₁: CH₂F (3) S Pyrimidinyl NH—C(O) Imidazolyl Z₁:CHF₂ (2) S Pyrimidinyl NH—C(O) Imidazolyl Z₁: CHF₂ (3) S PyrimidinylNH—C(O) Imidazolyl Z₁: CF₃ (2) S Pyrimidinyl NH—C(O) Imidazolyl Z₁: CF₃(3) S Pyrimidinyl NH—C(O) Imidazolyl Z₁: CH₂—CH₂F (2) S PyrimidinylNH—C(O) Imidazolyl Z₁: CH₂—CH₂F (3) S Pyrimidinyl NH—C(O) Imidazolyl Z₁:CH₂—CHF₂ (2) S Pyrimidinyl NH—C(O) Imidazolyl Z₁: CH₂—CHF₂ (3) SPyrimidinyl NH—C(O) Imidazolyl Z₁: CH₂—CF₃ (2) S Pyrimidinyl NH—C(O)Imidazolyl Z₁: CH₂—CF₃ (3) S Pyrimidinyl NH—C(O) Furanyl None SPyrimidinyl NH—C(O) Furanyl Z₁: F (2) S Pyrimidinyl NH—C(O) Furanyl Z₁:F (3) S Pyrimidinyl NH—C(O) Furanyl Z₁: F (2) Z₂: F (3) S PyrimidinylNH—C(O) Furanyl Z₁: Cl (2) S Pyrimidinyl NH—C(O) Furanyl Z₁: Cl (3) SPyrimidinyl NH—C(O) Furanyl Z₁: Cl (2) Z₂: Cl (3) S Pyrimidinyl NH—C(O)Furanyl Z₁: F (2) Z₂: Cl (3) S Pyrimidinyl NH—C(O) Furanyl Z₁: Cl (2)Z₂: F (3) S Pyrimidinyl NH—C(O) Furanyl Z₁: CH₃ (2) S PyrimidinylNH—C(O) Furanyl Z₁: CH₃ (3) S Pyrimidinyl NH—C(O) Furanyl Z₁: CH₂—CH₃(2) S Pyrimidinyl NH—C(O) Furanyl Z₁: CH₂—CH₃ (3) S Pyrimidinyl NH—C(O)Furanyl Z₁: CH₂—CH₂—CH₃ or iPr (2) S Pyrimidinyl NH—C(O) Furanyl Z₁:CH₂—CH₂—CH₃ or iPr (3) S Pyrimidinyl NH—C(O) Furanyl Z₁: CH₂F (2) SPyrimidinyl NH—C(O) Furanyl Z₁: CH₂F (3) S Pyrimidinyl NH—C(O) FuranylZ₁: CHF₂ (2) S Pyrimidinyl NH—C(O) Furanyl Z₁: CHF₂ (3) S PyrimidinylNH—C(O) Furanyl Z₁: CF₃ (2) S Pyrimidinyl NH—C(O) Furanyl Z₁: CF₃ (3) SPyrimidinyl NH—C(O) Furanyl Z₁: CH₂—CH₂F (2) S Pyrimidinyl NH—C(O)Furanyl Z₁: CH₂—CH₂F (3) S Pyrimidinyl NH—C(O) Furanyl Z₁: CH₂—CHF₂ (2)S Pyrimidinyl NH—C(O) Furanyl Z₁: CH₂—CHF₂ (3) S Pyrimidinyl NH—C(O)Furanyl Z₁: CH₂—CF₃ (2) S Pyrimidinyl NH—C(O) Furanyl Z₁: CH₂—CF₃ (3) SPyrimidinyl NH—C(O) Oxazolyl None S Pyrimidinyl NH—C(O) Oxazolyl Z₁: F(2) S Pyrimidinyl NH—C(O) Oxazolyl Z₁: F (3) S Pyrimidinyl NH—C(O)Oxazolyl Z₁: F (2) Z₂: F (3) S Pyrimidinyl NH—C(O) Oxazolyl Z₁: Cl (2) SPyrimidinyl NH—C(O) Oxazolyl Z₁: Cl (3) S Pyrimidinyl NH—C(O) OxazolylZ₁: Cl (2) Z₂: Cl (3) S Pyrimidinyl NH—C(O) Oxazolyl Z₁: F (2) Z₂: Cl(3) S Pyrimidinyl NH—C(O) Oxazolyl Z₁: Cl (2) Z₂: F (3) S PyrimidinylNH—C(O) Oxazolyl Z₁: CH₃ (2) S Pyrimidinyl NH—C(O) Oxazolyl Z₁: CH₃ (3)S Pyrimidinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₃ (2) S Pyrimidinyl NH—C(O)Oxazolyl Z₁: CH₂—CH₃ (3) S Pyrimidinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₂—CH₃or iPr (2) S Pyrimidinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) SPyrimidinyl NH—C(O) Oxazolyl Z₁: CH₂F (2) S Pyrimidinyl NH—C(O) OxazolylZ₁: CH₂F (3) S Pyrimidinyl NH—C(O) Oxazolyl Z₁: CHF₂ (2) S PyrimidinylNH—C(O) Oxazolyl Z₁: CHF₂ (3) S Pyrimidinyl NH—C(O) Oxazolyl Z₁: CF₃ (2)S Pyrimidinyl NH—C(O) Oxazolyl Z₁: CF₃ (3) S Pyrimidinyl NH—C(O)Oxazolyl Z₁: CH₂—CH₂F (2) S Pyrimidinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₂F(3) S Pyrimidinyl NH—C(O) Oxazolyl Z₁: CH₂—CHF₂ (2) S PyrimidinylNH—C(O) Oxazolyl Z₁: CH₂—CHF₂ (3) S Pyrimidinyl NH—C(O) Oxazolyl Z₁:CH₂—CF₃ (2) S Pyrimidinyl NH—C(O) Oxazolyl Z₁: CH₂—CF₃ (3) S PyrimidinylNH—C(O) Thiophenyl None S Pyrimidinyl NH—C(O) Thiophenyl Z₁: F (2) SPyrimidinyl NH—C(O) Thiophenyl Z₁: F (3) S Pyrimidinyl NH—C(O)Thiophenyl Z₁: F (2) Z₂: F (3) S Pyrimidinyl NH—C(O) Thiophenyl Z₁: Cl(2) S Pyrimidinyl NH—C(O) Thiophenyl Z₁: Cl (3) S Pyrimidinyl NH—C(O)Thiophenyl Z₁: Cl (2) Z₂: Cl (3) S Pyrimidinyl NH—C(O) Thiophenyl Z₁: F(2) Z₂: Cl (3) S Pyrimidinyl NH—C(O) Thiophenyl Z₁: Cl (2) Z₂: F (3) SPyrimidinyl NH—C(O) Thiophenyl Z₁: CH₃ (2) S Pyrimidinyl NH—C(O)Thiophenyl Z₁: CH₃ (3) S Pyrimidinyl NH—C(O) Thiophenyl Z₁: CH₂—CH₃ (2)S Pyrimidinyl NH—C(O) Thiophenyl Z₁: CH₂—CH₃ (3) S Pyrimidinyl NH—C(O)Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (2) S Pyrimidinyl NH—C(O) ThiophenylZ₁: CH₂—CH₂—CH₃ or iPr (3) S Pyrimidinyl NH—C(O) Thiophenyl Z₁: CH₂F (2)S Pyrimidinyl NH—C(O) Thiophenyl Z₁: CH₂F (3) S Pyrimidinyl NH—C(O)Thiophenyl Z₁: CHF₂ (2) S Pyrimidinyl NH—C(O) Thiophenyl Z₁: CHF₂ (3) SPyrimidinyl NH—C(O) Thiophenyl Z₁: CF₃ (2) S Pyrimidinyl NH—C(O)Thiophenyl Z₁: CF₃ (3) S Pyrimidinyl NH—C(O) Thiophenyl Z₁: CH₂—CH₂F (2)S Pyrimidinyl NH—C(O) Thiophenyl Z₁: CH₂—CH₂F (3) S Pyrimidinyl NH—C(O)Thiophenyl Z₁: CH₂—CHF₂ (2) S Pyrimidinyl NH—C(O) Thiophenyl Z₁:CH₂—CHF₂ (3) S Pyrimidinyl NH—C(O) Thiophenyl Z₁: CH₂—CF₃ (2) SPyrimidinyl NH—C(O) Thiophenyl Z₁: CH₂—CF₃ (3) S Pyrimidinyl NH—C(O)Thiazolyl None S Pyrimidinyl NH—C(O) Thiazolyl Z₁: F (2) S PyrimidinylNH—C(O) Thiazolyl Z₁: F (3) S Pyrimidinyl NH—C(O) Thiazolyl Z₁: F (2)Z₂: F (3) S Pyrimidinyl NH—C(O) Thiazolyl Z₁: Cl (2) S PyrimidinylNH—C(O) Thiazolyl Z₁: Cl (3) S Pyrimidinyl NH—C(O) Thiazolyl Z₁: Cl (2)Z₂: Cl (3) S Pyrimidinyl NH—C(O) Thiazolyl Z₁: F (2) Z₂: Cl (3) SPyrimidinyl NH—C(O) Thiazolyl Z₁: Cl (2) Z₂: F (3) S Pyrimidinyl NH—C(O)Thiazolyl Z₁: CH₃ (2) S Pyrimidinyl NH—C(O) Thiazolyl Z₁: CH₃ (3) SPyrimidinyl NH—C(O) Thiazolyl Z₁: CH₂—CH₃ (2) S Pyrimidinyl NH—C(O)Thiazolyl Z₁: CH₂—CH₃ (3) S Pyrimidinyl NH—C(O) Thiazolyl Z₁:CH₂—CH₂—CH₃ or iPr (2) S Pyrimidinyl NH—C(O) Thiazolyl Z₁: CH₂—CH₂—CH₃or iPr (3) S Pyrimidinyl NH—C(O) Thiazolyl Z₁: CH₂F (2) S PyrimidinylNH—C(O) Thiazolyl Z₁: CH₂F (3) S Pyrimidinyl NH—C(O) Thiazolyl Z₁: CHF₂(2) S Pyrimidinyl NH—C(O) Thiazolyl Z₁: CHF₂ (3) S Pyrimidinyl NH—C(O)Thiazolyl Z₁: CF₃ (2) S Pyrimidinyl NH—C(O) Thiazolyl Z₁: CF₃ (3) SPyrimidinyl NH—C(O) Thiazolyl Z₁: CH₂—CH₂F (2) S Pyrimidinyl NH—C(O)Thiazolyl Z₁: CH₂—CH₂F (3) S Pyrimidinyl NH—C(O) Thiazolyl Z₁: CH₂—CHF₂(2) S Pyrimidinyl NH—C(O) Thiazolyl Z₁: CH₂—CHF₂ (3) S PyrimidinylNH—C(O) Thiazolyl Z₁: CH₂—CF₃ (2) S Pyrimidinyl NH—C(O) Thiazolyl Z₁:CH₂—CF₃ (3) S Pyrimidinyl NH—SO₂ Phenyl None S Pyrimidinyl NH—SO₂ PhenylZ₁: F (para) S Pyrimidinyl NH—SO₂ phenyl Z₁: F (meta) S PyrimidinylNH—SO₂ phenyl Z₁: F (ortho) S Pyrimidinyl NH—SO₂ phenyl Z₁: F (para) Z₂:F (meta) S Pyrimidinyl NH—SO₂ Phenyl Z₁: Cl (meta) S Pyrimidinyl NH—SO₂Phenyl Z₁: Cl (para) S Pyrimidinyl NH—SO₂ Phenyl Z₁: Cl (para) Z₂: Cl(meta) S Pyrimidinyl NH—SO₂ Phenyl Z₁: F (para) Z₂: Cl (meta) SPyrimidinyl NH—SO₂ Phenyl Z₁: Cl (para) Z₂: F (meta) S PyrimidinylNH—SO₂ Phenyl Z₁: CH₃ (para) S Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₃ (meta)S Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₃ (ortho) S Pyrimidinyl NH—SO₂ PhenylZ₁: CH₂—CH₃ (para) S Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₂—CH₃ (meta) SPyrimidinyl NH—SO₂ Phenyl Z₁: CH₂—CH₃ (ortho) S Pyrimidinyl NH—SO₂Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (para) S Pyrimidinyl NH—SO₂ Phenyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) S Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂—CH₃ oriPr (ortho) S Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₂F (para) S PyrimidinylNH—SO₂ Phenyl Z₁: CH₂F (meta) S Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₂F(ortho) S Pyrimidinyl NH—SO₂ Phenyl Z₁: CHF₂ (para) S Pyrimidinyl NH—SO₂Phenyl Z₁: CHF₂ (meta) S Pyrimidinyl NH—SO₂ Phenyl Z₁: CHF₂ (ortho) SPyrimidinyl NH—SO₂ Phenyl Z₁: CF₃ (para) S Pyrimidinyl NH—SO₂ Phenyl Z₁:CF₃ (meta) S Pyrimidinyl NH—SO₂ Phenyl Z₁: CF₃ (ortho) S PyrimidinylNH—SO₂ Phenyl Z₁: CH₂—CH₂F (para) S Pyrimidinyl NH—SO₂ Phenyl Z₁:CH₂—CH₂F (meta) S Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂F (ortho) SPyrimidinyl NH—SO₂ Phenyl Z₁: CH₂—CHF₂ (para) S Pyrimidinyl NH—SO₂Phenyl Z₁: CH₂—CHF₂ (meta) S Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₂—CHF₂(ortho) S Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₂—CF₃ (para) S PyrimidinylNH—SO₂ Phenyl Z₁: CH₂—CF₃ (meta) S Pyrimidinyl NH—SO₂ Phenyl Z₁: CH₂—CF₃(ortho) S Pyrimidinyl NH—SO₂ Pyridinyl None S Pyrimidinyl NH—SO₂Pyridinyl Z₁: F (para) S Pyrimidinyl NH—SO₂ Pyridinyl Z₁: F (meta) SPyrimidinyl NH—SO₂ Pyridinyl Z₁: F (ortho) S Pyrimidinyl NH—SO₂Pyridinyl Z₁: F (para) Z₂: F (meta) S Pyrimidinyl NH—SO₂ Pyridinyl Z₁:Cl (meta) S Pyrimidinyl NH—SO₂ Pyridinyl Z₁: Cl (para) S PyrimidinylNH—SO₂ Pyridinyl Z₁: Cl (para) Z₂: Cl (meta) S Pyrimidinyl NH—SO₂Pyridinyl Z₁: F (para) Z₂: Cl (meta) S Pyrimidinyl NH—SO₂ Pyridinyl Z₁:Cl (para) Z₂: F (meta) S Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₃ (para) SPyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₃ (meta) S Pyrimidinyl NH—SO₂Pyridinyl Z₁: CH₃ (ortho) S Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₃(para) S Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₃ (meta) S PyrimidinylNH—SO₂ Pyridinyl Z₁: CH₂—CH₃ (ortho) S Pyrimidinyl NH—SO₂ Pyridinyl Z₁:CH₂—CH₂—CH₃ or iPr (para) S Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₂—CH₃or iPr (meta) S Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr(ortho) S Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₂F (para) S PyrimidinylNH—SO₂ Pyridinyl Z₁: CH₂F (meta) S Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₂F(ortho) S Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CHF₂ (para) S PyrimidinylNH—SO₂ Pyridinyl Z₁: CHF₂ (meta) S Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CHF₂(ortho) S Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CF₃ (para) S PyrimidinylNH—SO₂ Pyridinyl Z₁: CF₃ (meta) S Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CF₃(ortho) S Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₂F (para) S PyrimidinylNH—SO₂ Pyridinyl Z₁: CH₂—CH₂F (meta) S Pyrimidinyl NH—SO₂ Pyridinyl Z₁:CH₂—CH₂F (ortho) S Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₂—CHF₂ (para) SPyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₂—CHF₂ (meta) S Pyrimidinyl NH—SO₂Pyridinyl Z₁: CH₂—CHF₂ (ortho) S Pyrimidinyl NH—SO₂ Pyridinyl Z₁:CH₂—CF₃ (para) S Pyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₂—CF₃ (meta) SPyrimidinyl NH—SO₂ Pyridinyl Z₁: CH₂—CF₃ (ortho) S Pyrimidinyl NH—SO₂Pyrimidinyl None S Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: F (para) SPyrimidinyl NH—SO₂ Pyrimidinyl Z₁: F (meta) S Pyrimidinyl NH—SO₂Pyrimidinyl Z₁: F (ortho) S Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: F (para)Z₂: F (meta) S Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: Cl (meta) SPyrimidinyl NH—SO₂ Pyrimidinyl Z₁: Cl (para) S Pyrimidinyl NH—SO₂Pyrimidinyl Z₁: Cl (para) Z₂: Cl (meta) S Pyrimidinyl NH—SO₂ PyrimidinylZ₁: F (para) Z₂: Cl (meta) S Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: Cl(para) Z₂: F (meta) S Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₃ (para) SPyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₃ (meta) S Pyrimidinyl NH—SO₂Pyrimidinyl Z₁: CH₃ (ortho) S Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₃(para) S Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₃ (meta) S PyrimidinylNH—SO₂ Pyrimidinyl Z₁: CH₂—CH₃ (ortho) S Pyrimidinyl NH—SO₂ PyrimidinylZ₁: CH₂—CH₂—CH₃ or iPr (para) S Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) S Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) S Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₂F(para) S Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₂F (meta) S PyrimidinylNH—SO₂ Pyrimidinyl Z₁: CH₂F (ortho) S Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁:CHF₂ (para) S Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CHF₂ (meta) SPyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CHF₂ (ortho) S Pyrimidinyl NH—SO₂Pyrimidinyl Z₁: CF₃ (para) S Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CF₃(meta) S Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CF₃ (ortho) S PyrimidinylNH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂F (para) S Pyrimidinyl NH—SO₂ PyrimidinylZ₁: CH₂—CH₂F (meta) S Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂F(ortho) S Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CHF₂ (para) SPyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CHF₂ (meta) S Pyrimidinyl NH—SO₂Pyrimidinyl Z₁: CH₂—CHF₂ (ortho) S Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁:CH₂—CF₃ (para) S Pyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CF₃ (meta) SPyrimidinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CF₃ (ortho) S Pyrimidinyl NH—SO₂Pyrazinyl None S Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: F (para) S PyrimidinylNH—SO₂ Pyrazinyl Z₁: F (meta) S Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: F(ortho) S Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: F (para) Z₂: F (meta) SPyrimidinyl NH—SO₂ Pyrazinyl Z₁: Cl (meta) S Pyrimidinyl NH—SO₂Pyrazinyl Z₁: Cl (para) S Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: Cl (para) Z₂:Cl (meta) S Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: F (para) Z₂: Cl (meta) SPyrimidinyl NH—SO₂ Pyrazinyl Z₁: Cl (para) Z₂: F (meta) S PyrimidinylNH—SO₂ Pyrazinyl Z₁: CH₃ (para) S Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₃(meta) S Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₃ (ortho) S PyrimidinylNH—SO₂ Pyrazinyl Z₁: CH₂—CH₃ (para) S Pyrimidinyl NH—SO₂ Pyrazinyl Z₁:CH₂—CH₃ (meta) S Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₃ (ortho) SPyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) S PyrimidinylNH—SO₂ Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) S Pyrimidinyl NH—SO₂Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) S Pyrimidinyl NH—SO₂ PyrazinylZ₁: CH₂F (para) S Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₂F (meta) SPyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₂F (ortho) S Pyrimidinyl NH—SO₂Pyrazinyl Z₁: CHF₂ (para) S Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CHF₂ (meta)S Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CHF₂ (ortho) S Pyrimidinyl NH—SO₂Pyrazinyl Z₁: CF₃ (para) S Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CF₃ (meta) SPyrimidinyl NH—SO₂ Pyrazinyl Z₁: CF₃ (ortho) S Pyrimidinyl NH—SO₂Pyrazinyl Z₁: CH₂—CH₂F (para) S Pyrimidinyl NH—SO₂ Pyrazinyl Z₁:CH₂—CH₂F (meta) S Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₂F (ortho) SPyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CHF₂ (para) S Pyrimidinyl NH—SO₂Pyrazinyl Z₁: CH₂—CHF₂ (meta) S Pyrimidinyl NH—SO₂ Pyrazinyl Z₁:CH₂—CHF₂ (ortho) S Pyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CF₃ (para) SPyrimidinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CF₃ (meta) S Pyrimidinyl NH—SO₂Pyrazinyl Z₁: CH₂—CF₃ (ortho) S Pyrimidinyl NH—SO₂ Pyrrolyl None SPyrimidinyl NH—SO₂ Pyrrolyl Z₁: F (2) S Pyrimidinyl NH—SO₂ Pyrrolyl Z₁:F (3) S Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: F (2) Z₂: F (3) S PyrimidinylNH—SO₂ Pyrrolyl Z₁: Cl (2) S Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: Cl (3) SPyrimidinyl NH—SO₂ Pyrrolyl Z₁: Cl (2) Z₂: Cl (3) S Pyrimidinyl NH—SO₂Pyrrolyl Z₁: F (2) Z₂: Cl (3) S Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: Cl (2)Z₂: F (3) S Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: CH₃ (2) S Pyrimidinyl NH—SO₂Pyrrolyl Z₁: CH₃ (3) S Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CH₃ (2) SPyrimidinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CH₃ (3) S Pyrimidinyl NH—SO₂Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) S Pyrimidinyl NH—SO₂ Pyrrolyl Z₁:CH₂—CH₂—CH₃ or iPr (3) S Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: CH₂F (2) SPyrimidinyl NH—SO₂ Pyrrolyl Z₁: CH₂F (3) S Pyrimidinyl NH—SO₂ PyrrolylZ₁: CHF₂ (2) S Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: CHF₂ (3) S PyrimidinylNH—SO₂ Pyrrolyl Z₁: CF₃ (2) S Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: CF₃ (3) SPyrimidinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CH₂F (2) S Pyrimidinyl NH—SO₂Pyrrolyl Z₁: CH₂—CH₂F (3) S Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CHF₂ (2)S Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CHF₂ (3) S Pyrimidinyl NH—SO₂Pyrrolyl Z₁: CH₂—CF₃ (2) S Pyrimidinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CF₃ (3) SPyrimidinyl NH—SO₂ Imidazolyl None S Pyrimidinyl NH—SO₂ Imidazolyl Z₁: F(2) S Pyrimidinyl NH—SO₂ Imidazolyl Z₁: F (3) S Pyrimidinyl NH—SO₂Imidazolyl Z₁: F (2) Z₂: F (3) S Pyrimidinyl NH—SO₂ Imidazolyl Z₁: Cl(2) S Pyrimidinyl NH—SO₂ Imidazolyl Z₁: Cl (3) S Pyrimidinyl NH—SO₂Imidazolyl Z₁: Cl (2) Z₂: Cl (3) S Pyrimidinyl NH—SO₂ Imidazolyl Z₁: F(2) Z₂: Cl (3) S Pyrimidinyl NH—SO₂ Imidazolyl Z₁: Cl (2) Z₂: F (3) SPyrimidinyl NH—SO₂ Imidazolyl Z₁: CH₃ (2) S Pyrimidinyl NH—SO₂Imidazolyl Z₁: CH₃ (3) S Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₃ (2) SPyrimidinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₃ (3) S Pyrimidinyl NH—SO₂Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) S Pyrimidinyl NH—SO₂ ImidazolylZ₁: CH₂—CH₂—CH₃ or iPr (3) S Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CH₂F (2)S Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CH₂F (3) S Pyrimidinyl NH—SO₂Imidazolyl Z₁: CHF₂ (2) S Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CHF₂ (3) SPyrimidinyl NH—SO₂ Imidazolyl Z₁: CF₃ (2) S Pyrimidinyl NH—SO₂Imidazolyl Z₁: CF₃ (3) S Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₂F (2)S Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₂F (3) S Pyrimidinyl NH—SO₂Imidazolyl Z₁: CH₂—CHF₂ (2) S Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CH₂—CHF₂(3) S Pyrimidinyl NH—SO₂ Imidazolyl Z₁: CH₂—CF₃ (2) S Pyrimidinyl NH—SO₂Imidazolyl Z₁: CH₂—CF₃ (3) S Pyrimidinyl NH—SO₂ Furanyl None SPyrimidinyl NH—SO₂ Furanyl Z₁: F (2) S Pyrimidinyl NH—SO₂ Furanyl Z₁: F(3) S Pyrimidinyl NH—SO₂ Furanyl Z₁: F (2) Z₂: F (3) S PyrimidinylNH—SO₂ Furanyl Z₁: Cl (2) S Pyrimidinyl NH—SO₂ Furanyl Z₁: Cl (3) SPyrimidinyl NH—SO₂ Furanyl Z₁: Cl (2) Z₂: Cl (3) S Pyrimidinyl NH—SO₂Furanyl Z₁: F (2) Z₂: Cl (3) S Pyrimidinyl NH—SO₂ Furanyl Z₁: Cl (2) Z₂:F (3) S Pyrimidinyl NH—SO₂ Furanyl Z₁: CH₃ (2) S Pyrimidinyl NH—SO₂Furanyl Z₁: CH₃ (3) S Pyrimidinyl NH—SO₂ Furanyl Z₁: CH₂—CH₃ (2) SPyrimidinyl NH—SO₂ Furanyl Z₁: CH₂—CH₃ (3) S Pyrimidinyl NH—SO₂ FuranylZ₁: CH₂—CH₂—CH₃ or iPr (2) S Pyrimidinyl NH—SO₂ Furanyl Z₁: CH₂—CH₂—CH₃or iPr (3) S Pyrimidinyl NH—SO₂ Furanyl Z₁: CH₂F (2) S PyrimidinylNH—SO₂ Furanyl Z₁: CH₂F (3) S Pyrimidinyl NH—SO₂ Furanyl Z₁: CHF₂ (2) SPyrimidinyl NH—SO₂ Furanyl Z₁: CHF₂ (3) S Pyrimidinyl NH—SO₂ Furanyl Z₁:CF₃ (2) S Pyrimidinyl NH—SO₂ Furanyl Z₁: CF₃ (3) S Pyrimidinyl NH—SO₂Furanyl Z₁: CH₂—CH₂F (2) S Pyrimidinyl NH—SO₂ Furanyl Z₁: CH₂—CH₂F (3) SPyrimidinyl NH—SO₂ Furanyl Z₁: CH₂—CHF₂ (2) S Pyrimidinyl NH—SO₂ FuranylZ₁: CH₂—CHF₂ (3) S Pyrimidinyl NH—SO₂ Furanyl Z₁: CH₂—CF₃ (2) SPyrimidinyl NH—SO₂ Furanyl Z₁: CH₂—CF₃ (3) S Pyrimidinyl NH—SO₂ OxazolylNone S Pyrimidinyl NH—SO₂ Oxazolyl Z₁: F (2) S Pyrimidinyl NH—SO₂Oxazolyl Z₁: F (3) S Pyrimidinyl NH—SO₂ Oxazolyl Z₁: F (2) Z₂: F (3) SPyrimidinyl NH—SO₂ Oxazolyl Z₁: Cl (2) S Pyrimidinyl NH—SO₂ Oxazolyl Z₁:Cl (3) S Pyrimidinyl NH—SO₂ Oxazolyl Z₁: Cl (2) Z₂: Cl (3) S PyrimidinylNH—SO₂ Oxazolyl Z₁: F (2) Z₂: Cl (3) S Pyrimidinyl NH—SO₂ Oxazolyl Z₁:Cl (2) Z₂: F (3) S Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CH₃ (2) S PyrimidinylNH—SO₂ Oxazolyl Z₁: CH₃ (3) S Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CH₂—CH₃(2) S Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CH₂—CH₃ (3) S Pyrimidinyl NH—SO₂Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) S Pyrimidinyl NH—SO₂ Oxazolyl Z₁:CH₂—CH₂—CH₃ or iPr (3) S Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CH₂F (2) SPyrimidinyl NH—SO₂ Oxazolyl Z₁: CH₂F (3) S Pyrimidinyl NH—SO₂ OxazolylZ₁: CHF₂ (2) S Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CHF₂ (3) S PyrimidinylNH—SO₂ Oxazolyl Z₁: CF₃ (2) S Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CF₃ (3) SPyrimidinyl NH—SO₂ Oxazolyl Z₁: CH₂—CH₂F (2) S Pyrimidinyl NH—SO₂Oxazolyl Z₁: CH₂—CH₂F (3) S Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CH₂—CHF₂ (2)S Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CH₂—CHF₂ (3) S Pyrimidinyl NH—SO₂Oxazolyl Z₁: CH₂—CF₃ (2) S Pyrimidinyl NH—SO₂ Oxazolyl Z₁: CH₂—CF₃ (3) SPyrimidinyl NH—SO₂ Thiophenyl None S Pyrimidinyl NH—SO₂ Thiophenyl Z₁: F(2) S Pyrimidinyl NH—SO₂ Thiophenyl Z₁: F (3) S Pyrimidinyl NH—SO₂Thiophenyl Z₁: F (2) Z₂: F (3) S Pyrimidinyl NH—SO₂ Thiophenyl Z₁: Cl(2) S Pyrimidinyl NH—SO₂ Thiophenyl Z₁: Cl (3) S Pyrimidinyl NH—SO₂Thiophenyl Z₁: Cl (2) Z₂: Cl (3) S Pyrimidinyl NH—SO₂ Thiophenyl Z₁: F(2) Z₂: Cl (3) S Pyrimidinyl NH—SO₂ Thiophenyl Z₁: Cl (2) Z₂: F (3) SPyrimidinyl NH—SO₂ Thiophenyl Z₁: CH₃ (2) S Pyrimidinyl NH—SO₂Thiophenyl Z₁: CH₃ (3) S Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₃ (2) SPyrimidinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₃ (3) S Pyrimidinyl NH—SO₂Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (2) S Pyrimidinyl NH—SO₂ ThiophenylZ₁: CH₂—CH₂—CH₃ or iPr (3) S Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CH₂F (2)S Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CH₂F (3) S Pyrimidinyl NH—SO₂Thiophenyl Z₁: CHF₂ (2) S Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CHF₂ (3) SPyrimidinyl NH—SO₂ Thiophenyl Z₁: CF₃ (2) S Pyrimidinyl NH—SO₂Thiophenyl Z₁: CF₃ (3) S Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₂F (2)S Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₂F (3) S Pyrimidinyl NH—SO₂Thiophenyl Z₁: CH₂—CHF₂ (2) S Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CH₂—CHF₂(3) S Pyrimidinyl NH—SO₂ Thiophenyl Z₁: CH₂—CF₃ (2) S Pyrimidinyl NH—SO₂Thiophenyl Z₁: CH₂—CF₃ (3) S Pyrimidinyl NH—SO₂ Thiazolyl None SPyrimidinyl NH—SO₂ Thiazolyl Z₁: F (2) S Pyrimidinyl NH—SO₂ ThiazolylZ₁: F (3) S Pyrimidinyl NH—SO₂ Thiazolyl Z₁: F (2) Z₂: F (3) SPyrimidinyl NH—SO₂ Thiazolyl Z₁: Cl (2) S Pyrimidinyl NH—SO₂ ThiazolylZ₁: Cl (3) S Pyrimidinyl NH—SO₂ Thiazolyl Z₁: Cl (2) Z₂: Cl (3) SPyrimidinyl NH—SO₂ Thiazolyl Z₁: F (2) Z₂: Cl (3) S Pyrimidinyl NH—SO₂Thiazolyl Z₁: Cl (2) Z₂: F (3) S Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CH₃(2) S Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CH₃ (3) S Pyrimidinyl NH—SO₂Thiazolyl Z₁: CH₂—CH₃ (2) S Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₃ (3)S Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) S PyrimidinylNH—SO₂ Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) S Pyrimidinyl NH—SO₂Thiazolyl Z₁: CH₂F (2) S Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CH₂F (3) SPyrimidinyl NH—SO₂ Thiazolyl Z₁: CHF₂ (2) S Pyrimidinyl NH—SO₂ ThiazolylZ₁: CHF₂ (3) S Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CF₃ (2) S PyrimidinylNH—SO₂ Thiazolyl Z₁: CF₃ (3) S Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₂F(2) S Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₂F (3) S Pyrimidinyl NH—SO₂Thiazolyl Z₁: CH₂—CHF₂ (2) S Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CH₂—CHF₂(3) S Pyrimidinyl NH—SO₂ Thiazolyl Z₁: CH₂—CF₃ (2) S Pyrimidinyl NH—SO₂Thiazolyl Z₁: CH₂—CF₃ (3) S Pyrazinyl NH—CH₂ Phenyl None S PyrazinylNH—CH₂ Phenyl Z₁: F (para) S Pyrazinyl NH—CH₂ phenyl Z₁: F (meta) SPyrazinyl NH—CH₂ phenyl Z₁: F (ortho) S Pyrazinyl NH—CH₂ phenyl Z₁: F(para) Z₂: F (meta) S Pyrazinyl NH—CH₂ Phenyl Z₁: Cl (meta) S PyrazinylNH—CH₂ Phenyl Z₁: Cl (para) S Pyrazinyl NH—CH₂ Phenyl Z₁: Cl (para) Z₂:Cl (meta) S Pyrazinyl NH—CH₂ Phenyl Z₁: F (para) Z₂: Cl (meta) SPyrazinyl NH—CH₂ Phenyl Z₁: Cl (para) Z₂: F (meta) S Pyrazinyl NH—CH₂Phenyl Z₁: CH₃ (para) S Pyrazinyl NH—CH₂ Phenyl Z₁: CH₃ (meta) SPyrazinyl NH—CH₂ Phenyl Z₁: CH₃ (ortho) S Pyrazinyl NH—CH₂ Phenyl Z₁:CH₂—CH₃ (para) S Pyrazinyl NH—CH₂ Phenyl Z₁: CH₂—CH₃ (meta) S PyrazinylNH—CH₂ Phenyl Z₁: CH₂—CH₃ (ortho) S Pyrazinyl NH—CH₂ Phenyl Z₁:CH₂—CH₂—CH₃ or iPr (para) S Pyrazinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂—CH₃ oriPr (meta) S Pyrazinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) SPyrazinyl NH—CH₂ Phenyl Z₁: CH₂F (para) S Pyrazinyl NH—CH₂ Phenyl Z₁:CH₂F (meta) S Pyrazinyl NH—CH₂ Phenyl Z₁: CH₂F (ortho) S PyrazinylNH—CH₂ Phenyl Z₁: CHF₂ (para) S Pyrazinyl NH—CH₂ Phenyl Z₁: CHF₂ (meta)S Pyrazinyl NH—CH₂ Phenyl Z₁: CHF₂ (ortho) S Pyrazinyl NH—CH₂ Phenyl Z₁:CF₃ (para) S Pyrazinyl NH—CH₂ Phenyl Z₁: CF₃ (meta) S Pyrazinyl NH—CH₂Phenyl Z₁: CF₃ (ortho) S Pyrazinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂F (para) SPyrazinyl NH—CH₂ Phenyl Z₁: CH₂—CH₂F (meta) S Pyrazinyl NH—CH₂ PhenylZ₁: CH₂—CH₂F (ortho) S Pyrazinyl NH—CH₂ Phenyl Z₁: CH₂—CHF₂ (para) SPyrazinyl NH—CH₂ Phenyl Z₁: CH₂—CHF₂ (meta) S Pyrazinyl NH—CH₂ PhenylZ₁: CH₂—CHF₂ (ortho) S Pyrazinyl NH—CH₂ Phenyl Z₁: CH₂—CF₃ (para) SPyrazinyl NH—CH₂ Phenyl Z₁: CH₂—CF₃ (meta) S Pyrazinyl NH—CH₂ Phenyl Z₁:CH₂—CF₃ (ortho) S Pyrazinyl NH—CH₂ Pyridinyl None S Pyrazinyl NH—CH₂Pyridinyl Z₁: F (para) S Pyrazinyl NH—CH₂ Pyridinyl Z₁: F (meta) SPyrazinyl NH—CH₂ Pyridinyl Z₁: F (ortho) S Pyrazinyl NH—CH₂ PyridinylZ₁: F (para) Z₂: F (meta) S Pyrazinyl NH—CH₂ Pyridinyl Z₁: Cl (meta) SPyrazinyl NH—CH₂ Pyridinyl Z₁: Cl (para) S Pyrazinyl NH—CH₂ PyridinylZ₁: Cl (para) Z₂: Cl (meta) S Pyrazinyl NH—CH₂ Pyridinyl Z₁: F (para)Z₂: Cl (meta) S Pyrazinyl NH—CH₂ Pyridinyl Z₁: Cl (para) Z₂: F (meta) SPyrazinyl NH—CH₂ Pyridinyl Z₁: CH₃ (para) S Pyrazinyl NH—CH₂ PyridinylZ₁: CH₃ (meta) S Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₃ (ortho) S PyrazinylNH—CH₂ Pyridinyl Z₁: CH₂—CH₃ (para) S Pyrazinyl NH—CH₂ Pyridinyl Z₁:CH₂—CH₃ (meta) S Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₃ (ortho) SPyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) S PyrazinylNH—CH₂ Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) S Pyrazinyl NH—CH₂Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) S Pyrazinyl NH—CH₂ PyridinylZ₁: CH₂F (para) S Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂F (meta) S PyrazinylNH—CH₂ Pyridinyl Z₁: CH₂F (ortho) S Pyrazinyl NH—CH₂ Pyridinyl Z₁: CHF₂(para) S Pyrazinyl NH—CH₂ Pyridinyl Z₁: CHF₂ (meta) S Pyrazinyl NH—CH₂Pyridinyl Z₁: CHF₂ (ortho) S Pyrazinyl NH—CH₂ Pyridinyl Z₁: CF₃ (para) SPyrazinyl NH—CH₂ Pyridinyl Z₁: CF₃ (meta) S Pyrazinyl NH—CH₂ PyridinylZ₁: CF₃ (ortho) S Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₂F (para) SPyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂—CH₂F (meta) S Pyrazinyl NH—CH₂Pyridinyl Z₁: CH₂—CH₂F (ortho) S Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂—CHF₂(para) S Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂—CHF₂ (meta) S PyrazinylNH—CH₂ Pyridinyl Z₁: CH₂—CHF₂ (ortho) S Pyrazinyl NH—CH₂ Pyridinyl Z₁:CH₂—CF₃ (para) S Pyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂—CF₃ (meta) SPyrazinyl NH—CH₂ Pyridinyl Z₁: CH₂—CF₃ (ortho) S Pyrazinyl NH—CH₂Pyrimidinyl None S Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: F (para) S PyrazinylNH—CH₂ Pyrimidinyl Z₁: F (meta) S Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: F(ortho) S Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: F (para) Z₂: F (meta) SPyrazinyl NH—CH₂ Pyrimidinyl Z₁: Cl (meta) S Pyrazinyl NH—CH₂Pyrimidinyl Z₁: Cl (para) S Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: Cl (para)Z₂: Cl (meta) S Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: F (para) Z₂: Cl (meta)S Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: Cl (para) Z₂: F (meta) S PyrazinylNH—CH₂ Pyrimidinyl Z₁: CH₃ (para) S Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₃(meta) S Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₃ (ortho) S Pyrazinyl NH—CH₂Pyrimidinyl Z₁: CH₂—CH₃ (para) S Pyrazinyl NH—CH₂ Pyrimidinyl Z₁:CH₂—CH₃ (meta) S Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₃ (ortho) SPyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) S PyrazinylNH—CH₂ Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) S Pyrazinyl NH—CH₂Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) S Pyrazinyl NH—CH₂Pyrimidinyl Z₁: CH₂F (para) S Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₂F(meta) S Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₂F (ortho) S PyrazinylNH—CH₂ Pyrimidinyl Z₁: CHF₂ (para) S Pyrazinyl NH—CH₂ Pyrimidinyl Z₁:CHF₂ (meta) S Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CHF₂ (ortho) S PyrazinylNH—CH₂ Pyrimidinyl Z₁: CF₃ (para) S Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CF₃(meta) S Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CF₃ (ortho) S Pyrazinyl NH—CH₂Pyrimidinyl Z₁: CH₂—CH₂F (para) S Pyrazinyl NH—CH₂ Pyrimidinyl Z₁:CH₂—CH₂F (meta) S Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CH₂F (ortho) SPyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CHF₂ (para) S Pyrazinyl NH—CH₂Pyrimidinyl Z₁: CH₂—CHF₂ (meta) S Pyrazinyl NH—CH₂ Pyrimidinyl Z₁:CH₂—CHF₂ (ortho) S Pyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CF₃ (para) SPyrazinyl NH—CH₂ Pyrimidinyl Z₁: CH₂—CF₃ (meta) S Pyrazinyl NH—CH₂Pyrimidinyl Z₁: CH₂—CF₃ (ortho) S Pyrazinyl NH—CH₂ Pyrazinyl None SPyrazinyl NH—CH₂ Pyrazinyl Z₁: F (para) S Pyrazinyl NH—CH₂ Pyrazinyl Z₁:F (meta) S Pyrazinyl NH—CH₂ Pyrazinyl Z₁: F (ortho) S Pyrazinyl NH—CH₂Pyrazinyl Z₁: F (para) Z₂: F (meta) S Pyrazinyl NH—CH₂ Pyrazinyl Z₁: Cl(meta) S Pyrazinyl NH—CH₂ Pyrazinyl Z₁: Cl (para) S Pyrazinyl NH—CH₂Pyrazinyl Z₁: Cl (para) Z₂: Cl (meta) S Pyrazinyl NH—CH₂ Pyrazinyl Z₁: F(para) Z₂: Cl (meta) S Pyrazinyl NH—CH₂ Pyrazinyl Z₁: Cl (para) Z₂: F(meta) S Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₃ (para) S Pyrazinyl NH—CH₂Pyrazinyl Z₁: CH₃ (meta) S Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₃ (ortho) SPyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₃ (para) S Pyrazinyl NH—CH₂Pyrazinyl Z₁: CH₂—CH₃ (meta) S Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₃(ortho) S Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) SPyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) S PyrazinylNH—CH₂ Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) S Pyrazinyl NH—CH₂Pyrazinyl Z₁: CH₂F (para) S Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂F (meta) SPyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂F (ortho) S Pyrazinyl NH—CH₂ PyrazinylZ₁: CHF₂ (para) S Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CHF₂ (meta) S PyrazinylNH—CH₂ Pyrazinyl Z₁: CHF₂ (ortho) S Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CF₃(para) S Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CF₃ (meta) S Pyrazinyl NH—CH₂Pyrazinyl Z₁: CF₃ (ortho) S Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₂F(para) S Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CH₂F (meta) S PyrazinylNH—CH₂ Pyrazinyl Z₁: CH₂—CH₂F (ortho) S Pyrazinyl NH—CH₂ Pyrazinyl Z₁:CH₂—CHF₂ (para) S Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CHF₂ (meta) SPyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CHF₂ (ortho) S Pyrazinyl NH—CH₂Pyrazinyl Z₁: CH₂—CF₃ (para) S Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CF₃(meta) S Pyrazinyl NH—CH₂ Pyrazinyl Z₁: CH₂—CF₃ (ortho) S PyrazinylNH—CH₂ Pyrrolyl None S Pyrazinyl NH—CH₂ Pyrrolyl Z₁: F (2) S PyrazinylNH—CH₂ Pyrrolyl Z₁: F (3) S Pyrazinyl NH—CH₂ Pyrrolyl Z₁: F (2) Z₂: F(3) S Pyrazinyl NH—CH₂ Pyrrolyl Z₁: Cl (2) S Pyrazinyl NH—CH₂ PyrrolylZ₁: Cl (3) S Pyrazinyl NH—CH₂ Pyrrolyl Z₁: Cl (2) Z₂: Cl (3) S PyrazinylNH—CH₂ Pyrrolyl Z₁: F (2) Z₂: Cl (3) S Pyrazinyl NH—CH₂ Pyrrolyl Z₁: Cl(2) Z₂: F (3) S Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CH₃ (2) S Pyrazinyl NH—CH₂Pyrrolyl Z₁: CH₃ (3) S Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₃ (2) SPyrazinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₃ (3) S Pyrazinyl NH—CH₂ PyrrolylZ₁: CH₂—CH₂—CH₃ or iPr (2) S Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₂—CH₃or iPr (3) S Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CH₂F (2) S Pyrazinyl NH—CH₂Pyrrolyl Z₁: CH₂F (3) S Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CHF₂ (2) SPyrazinyl NH—CH₂ Pyrrolyl Z₁: CHF₂ (3) S Pyrazinyl NH—CH₂ Pyrrolyl Z₁:CF₃ (2) S Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CF₃ (3) S Pyrazinyl NH—CH₂Pyrrolyl Z₁: CH₂—CH₂F (2) S Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CH₂F (3) SPyrazinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CHF₂ (2) S Pyrazinyl NH—CH₂ PyrrolylZ₁: CH₂—CHF₂ (3) S Pyrazinyl NH—CH₂ Pyrrolyl Z₁: CH₂—CF₃ (2) S PyrazinylNH—CH₂ Pyrrolyl Z₁: CH₂—CF₃ (3) S Pyrazinyl NH—CH₂ Imidazolyl None SPyrazinyl NH—CH₂ Imidazolyl Z₁: F (2) S Pyrazinyl NH—CH₂ Imidazolyl Z₁:F (3) S Pyrazinyl NH—CH₂ Imidazolyl Z₁: F (2) Z₂: F (3) S PyrazinylNH—CH₂ Imidazolyl Z₁: Cl (2) S Pyrazinyl NH—CH₂ Imidazolyl Z₁: Cl (3) SPyrazinyl NH—CH₂ Imidazolyl Z₁: Cl (2) Z₂: Cl (3) S Pyrazinyl NH—CH₂Imidazolyl Z₁: F (2) Z₂: Cl (3) S Pyrazinyl NH—CH₂ Imidazolyl Z₁: Cl (2)Z₂: F (3) S Pyrazinyl NH—CH₂ Imidazolyl Z₁: CH₃ (2) S Pyrazinyl NH—CH₂Imidazolyl Z₁: CH₃ (3) S Pyrazinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₃ (2) SPyrazinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₃ (3) S Pyrazinyl NH—CH₂Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) S Pyrazinyl NH—CH₂ Imidazolyl Z₁:CH₂—CH₂—CH₃ or iPr (3) S Pyrazinyl NH—CH₂ Imidazolyl Z₁: CH₂F (2) SPyrazinyl NH—CH₂ Imidazolyl Z₁: CH₂F (3) S Pyrazinyl NH—CH₂ ImidazolylZ₁: CHF₂ (2) S Pyrazinyl NH—CH₂ Imidazolyl Z₁: CHF₂ (3) S PyrazinylNH—CH₂ Imidazolyl Z₁: CF₃ (2) S Pyrazinyl NH—CH₂ Imidazolyl Z₁: CF₃ (3)S Pyrazinyl NH—CH₂ Imidazolyl Z₁: CH₂—CH₂F (2) S Pyrazinyl NH—CH₂Imidazolyl Z₁: CH₂—CH₂F (3) S Pyrazinyl NH—CH₂ Imidazolyl Z₁: CH₂—CHF₂(2) S Pyrazinyl NH—CH₂ Imidazolyl Z₁: CH₂—CHF₂ (3) S Pyrazinyl NH—CH₂Imidazolyl Z₁: CH₂—CF₃ (2) S Pyrazinyl NH—CH₂ Imidazolyl Z₁: CH₂—CF₃ (3)S Pyrazinyl NH—CH₂ Furanyl None S Pyrazinyl NH—CH₂ Furanyl Z₁: F (2) SPyrazinyl NH—CH₂ Furanyl Z₁: F (3) S Pyrazinyl NH—CH₂ Furanyl Z₁: F (2)Z₂: F (3) S Pyrazinyl NH—CH₂ Furanyl Z₁: Cl (2) S Pyrazinyl NH—CH₂Furanyl Z₁: Cl (3) S Pyrazinyl NH—CH₂ Furanyl Z₁: Cl (2) Z₂: Cl (3) SPyrazinyl NH—CH₂ Furanyl Z₁: F (2) Z₂: Cl (3) S Pyrazinyl NH—CH₂ FuranylZ₁: Cl (2) Z₂: F (3) S Pyrazinyl NH—CH₂ Furanyl Z₁: CH₃ (2) S PyrazinylNH—CH₂ Furanyl Z₁: CH₃ (3) S Pyrazinyl NH—CH₂ Furanyl Z₁: CH₂—CH₃ (2) SPyrazinyl NH—CH₂ Furanyl Z₁: CH₂—CH₃ (3) S Pyrazinyl NH—CH₂ Furanyl Z₁:CH₂—CH₂—CH₃ or iPr (3) S Pyrazinyl NH—CH₂ Furanyl Z₁: CH₂—CH₂—CH₃ or iPr(2) S Pyrazinyl NH—CH₂ Furanyl Z₁: CH₂F (2) S Pyrazinyl NH—CH₂ FuranylZ₁: CH₂F (3) S Pyrazinyl NH—CH₂ Furanyl Z₁: CHF₂ (2) S Pyrazinyl NH—CH₂Furanyl Z₁: CHF₂ (3) S Pyrazinyl NH—CH₂ Furanyl Z₁: CF₃ (2) S PyrazinylNH—CH₂ Furanyl Z₁: CF₃ (3) S Pyrazinyl NH—CH₂ Furanyl Z₁: CH₂—CH₂F (2) SPyrazinyl NH—CH₂ Furanyl Z₁: CH₂—CH₂F (3) S Pyrazinyl NH—CH₂ Furanyl Z₁:CH₂—CHF₂ (2) S Pyrazinyl NH—CH₂ Furanyl Z₁: CH₂—CHF₂ (3) S PyrazinylNH—CH₂ Furanyl Z₁: CH₂—CF₃ (2) S Pyrazinyl NH—CH₂ Furanyl Z₁: CH₂—CF₃(3) S Pyrazinyl NH—CH₂ Oxazolyl None S Pyrazinyl NH—CH₂ Oxazolyl Z₁: F(2) S Pyrazinyl NH—CH₂ Oxazolyl Z₁: F (3) S Pyrazinyl NH—CH₂ OxazolylZ₁: F (2) Z₂: F (3) S Pyrazinyl NH—CH₂ Oxazolyl Z₁: Cl (2) S PyrazinylNH—CH₂ Oxazolyl Z₁: Cl (3) S Pyrazinyl NH—CH₂ Oxazolyl Z₁: Cl (2) Z₂: Cl(3) S Pyrazinyl NH—CH₂ Oxazolyl Z₁: F (2) Z₂: Cl (3) S Pyrazinyl NH—CH₂Oxazolyl Z₁: Cl (2) Z₂: F (3) S Pyrazinyl NH—CH₂ Oxazolyl Z₁: CH₃ (2) SPyrazinyl NH—CH₂ Oxazolyl Z₁: CH₃ (3) S Pyrazinyl NH—CH₂ Oxazolyl Z₁:CH₂—CH₃ (2) S Pyrazinyl NH—CH₂ Oxazolyl Z₁: CH₂—CH₃ (3) S PyrazinylNH—CH₂ Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) S Pyrazinyl NH—CH₂ OxazolylZ₁: CH₂—CH₂—CH₃ or iPr (3) S Pyrazinyl NH—CH₂ Oxazolyl Z₁: CH₂F (2) SPyrazinyl NH—CH₂ Oxazolyl Z₁: CH₂F (3) S Pyrazinyl NH—CH₂ Oxazolyl Z₁:CHF₂ (2) S Pyrazinyl NH—CH₂ Oxazolyl Z₁: CHF₂ (3) S Pyrazinyl NH—CH₂Oxazolyl Z₁: CF₃ (2) S Pyrazinyl NH—CH₂ Oxazolyl Z₁: CF₃ (3) S PyrazinylNH—CH₂ Oxazolyl Z₁: CH₂—CH₂F (2) S Pyrazinyl NH—CH₂ Oxazolyl Z₁:CH₂—CH₂F (3) S Pyrazinyl NH—CH₂ Oxazolyl Z₁: CH₂—CHF₂ (2) S PyrazinylNH—CH₂ Oxazolyl Z₁: CH₂—CHF₂ (3) S Pyrazinyl NH—CH₂ Oxazolyl Z₁: CH₂—CF₃(2) S Pyrazinyl NH—CH₂ Oxazolyl Z₁: CH₂—CF₃ (3) S Pyrazinyl NH—CH₂Thiophenyl None S Pyrazinyl NH—CH₂ Thiophenyl Z₁: F (2) S PyrazinylNH—CH₂ Thiophenyl Z₁: F (3) S Pyrazinyl NH—CH₂ Thiophenyl Z₁: F (2) Z₂:F (3) S Pyrazinyl NH—CH₂ Thiophenyl Z₁: Cl (2) S Pyrazinyl NH—CH₂Thiophenyl Z₁: Cl (3) S Pyrazinyl NH—CH₂ Thiophenyl Z₁: Cl (2) Z₂: Cl(3) S Pyrazinyl NH—CH₂ Thiophenyl Z₁: F (2) Z₂: Cl (3) S PyrazinylNH—CH₂ Thiophenyl Z₁: Cl (2) Z₂: F (3) S Pyrazinyl NH—CH₂ Thiophenyl Z₁:CH₃ (2) S Pyrazinyl NH—CH₂ Thiophenyl Z₁: CH₃ (3) S Pyrazinyl NH—CH₂Thiophenyl Z₁: CH₂—CH₃ (2) S Pyrazinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₃ (3)S Pyrazinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (2) S PyrazinylNH—CH₂ Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (3) S Pyrazinyl NH—CH₂Thiophenyl Z₁: CH₂F (2) S Pyrazinyl NH—CH₂ Thiophenyl Z₁: CH₂F (3) SPyrazinyl NH—CH₂ Thiophenyl Z₁: CHF₂ (2) S Pyrazinyl NH—CH₂ ThiophenylZ₁: CHF₂ (3) S Pyrazinyl NH—CH₂ Thiophenyl Z₁: CF₃ (2) S PyrazinylNH—CH₂ Thiophenyl Z₁: CF₃ (3) S Pyrazinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₂F(2) S Pyrazinyl NH—CH₂ Thiophenyl Z₁: CH₂—CH₂F (3) S Pyrazinyl NH—CH₂Thiophenyl Z₁: CH₂—CHF₂ (2) S Pyrazinyl NH—CH₂ Thiophenyl Z₁: CH₂—CHF₂(3) S Pyrazinyl NH—CH₂ Thiophenyl Z₁: CH₂—CF₃ (2) S Pyrazinyl NH—CH₂Thiophenyl Z₁: CH₂—CF₃ (3) S Pyrazinyl NH—CH₂ Thiazolyl None S PyrazinylNH—CH₂ Thiazolyl Z₁: F (2) S Pyrazinyl NH—CH₂ Thiazolyl Z₁: F (3) SPyrazinyl NH—CH₂ Thiazolyl Z₁: F (2) Z₂: F (3) S Pyrazinyl NH—CH₂Thiazolyl Z₁: Cl (2) S Pyrazinyl NH—CH₂ Thiazolyl Z₁: Cl (3) S PyrazinylNH—CH₂ Thiazolyl Z₁: Cl (2) Z₂: Cl (3) S Pyrazinyl NH—CH₂ Thiazolyl Z₁:F (2) Z₂: Cl (3) S Pyrazinyl NH—CH₂ Thiazolyl Z₁: Cl (2) Z₂: F (3) SPyrazinyl NH—CH₂ Thiazolyl Z₁: CH₃ (2) S Pyrazinyl NH—CH₂ Thiazolyl Z₁:CH₃ (3) S Pyrazinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₃ (2) S Pyrazinyl NH—CH₂Thiazolyl Z₁: CH₂—CH₃ (3) S Pyrazinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₂—CH₃or iPr (2) S Pyrazinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) SPyrazinyl NH—CH₂ Thiazolyl Z₁: CH₂F (2) S Pyrazinyl NH—CH₂ Thiazolyl Z₁:CH₂F (3) S Pyrazinyl NH—CH₂ Thiazolyl Z₁: CHF₂ (2) S Pyrazinyl NH—CH₂Thiazolyl Z₁: CHF₂ (3) S Pyrazinyl NH—CH₂ Thiazolyl Z₁: CF₃ (2) SPyrazinyl NH—CH₂ Thiazolyl Z₁: CF₃ (3) S Pyrazinyl NH—CH₂ Thiazolyl Z₁:CH₂—CH₂F (2) S Pyrazinyl NH—CH₂ Thiazolyl Z₁: CH₂—CH₂F (3) S PyrazinylNH—CH₂ Thiazolyl Z₁: CH₂—CHF₂ (2) S Pyrazinyl NH—CH₂ Thiazolyl Z₁:CH₂—CHF₂ (3) S Pyrazinyl NH—CH₂ Thiazolyl Z₁: CH₂—CF₃ (2) S PyrazinylNH—CH₂ Thiazolyl Z₁: CH₂—CF₃ (3) S Pyrazinyl NH—C(O) Phenyl None SPyrazinyl NH—C(O) Phenyl Z₁: F (para) S Pyrazinyl NH—C(O) phenyl Z₁: F(meta) S Pyrazinyl NH—C(O) phenyl Z₁: F (ortho) S Pyrazinyl NH—C(O)phenyl Z₁: F (para) Z₂: F (meta) S Pyrazinyl NH—C(O) Phenyl Z₁: Cl(meta) S Pyrazinyl NH—C(O) Phenyl Z₁: Cl (para) S Pyrazinyl NH—C(O)Phenyl Z₁: Cl (para) Z₂: Cl (meta) S Pyrazinyl NH—C(O) Phenyl Z₁: F(para) Z₂: Cl (meta) S Pyrazinyl NH—C(O) Phenyl Z₁: Cl (para) Z₂: F(meta) S Pyrazinyl NH—C(O) Phenyl Z₁: CH₃ (para) S Pyrazinyl NH—C(O)Phenyl Z₁: CH₃ (meta) S Pyrazinyl NH—C(O) Phenyl Z₁: CH₃ (ortho) SPyrazinyl NH—C(O) Phenyl Z₁: CH₂—CH₃ (para) S Pyrazinyl NH—C(O) PhenylZ₁: CH₂—CH₃ (meta) S Pyrazinyl NH—C(O) Phenyl Z₁: CH₂—CH₃ (ortho) SPyrazinyl NH—C(O) Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (para) S PyrazinylNH—C(O) Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) S Pyrazinyl NH—C(O) PhenylZ₁: CH₂—CH₂—CH₃ or iPr (ortho) S Pyrazinyl NH—C(O) Phenyl Z₁: CH₂F(para) S Pyrazinyl NH—C(O) Phenyl Z₁: CH₂F (meta) S Pyrazinyl NH—C(O)Phenyl Z₁: CH₂F (ortho) S Pyrazinyl NH—C(O) Phenyl Z₁: CHF₂ (para) SPyrazinyl NH—C(O) Phenyl Z₁: CHF₂ (meta) S Pyrazinyl NH—C(O) Phenyl Z₁:CHF₂ (ortho) S Pyrazinyl NH—C(O) Phenyl Z₁: CF₃ (para) S PyrazinylNH—C(O) Phenyl Z₁: CF₃ (meta) S Pyrazinyl NH—C(O) Phenyl Z₁: CF₃ (ortho)S Pyrazinyl NH—C(O) Phenyl Z₁: CH₂—CH₂F (para) S Pyrazinyl NH—C(O)Phenyl Z₁: CH₂—CH₂F (meta) S Pyrazinyl NH—C(O) Phenyl Z₁: CH₂—CH₂F(ortho) S Pyrazinyl NH—C(O) Phenyl Z₁: CH₂—CHF₂ (para) S PyrazinylNH—C(O) Phenyl Z₁: CH₂—CHF₂ (meta) S Pyrazinyl NH—C(O) Phenyl Z₁:CH₂—CHF₂ (ortho) S Pyrazinyl NH—C(O) Phenyl Z₁: CH₂—CF₃ (para) SPyrazinyl NH—C(O) Phenyl Z₁: CH₂—CF₃ (meta) S Pyrazinyl NH—C(O) PhenylZ₁: CH₂—CF₃ (ortho) S Pyrazinyl NH—C(O) Pyridinyl None S PyrazinylNH—C(O) Pyridinyl Z₁: F (para) S Pyrazinyl NH—C(O) Pyridinyl Z₁: F(meta) S Pyrazinyl NH—C(O) Pyridinyl Z₁: F (ortho) S Pyrazinyl NH—C(O)Pyridinyl Z₁: F (para) Z₂: F (meta) S Pyrazinyl NH—C(O) Pyridinyl Z₁: Cl(meta) S Pyrazinyl NH—C(O) Pyridinyl Z₁: Cl (para) S Pyrazinyl NH—C(O)Pyridinyl Z₁: Cl (para) Z₂: Cl (meta) S Pyrazinyl NH—C(O) Pyridinyl Z₁:F (para) Z₂: Cl (meta) S Pyrazinyl NH—C(O) Pyridinyl Z₁: Cl (para) Z₂: F(meta) S Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₃ (para) S Pyrazinyl NH—C(O)Pyridinyl Z₁: CH₃ (meta) S Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₃ (ortho) SPyrazinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₃ (para) S Pyrazinyl NH—C(O)Pyridinyl Z₁: CH₂—CH₃ (meta) S Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₃(ortho) S Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) SPyrazinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) S PyrazinylNH—C(O) Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) S Pyrazinyl NH—C(O)Pyridinyl Z₁: CH₂F (para) S Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₂F (meta)S Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₂F (ortho) S Pyrazinyl NH—C(O)Pyridinyl Z₁: CHF₂ (para) S Pyrazinyl NH—C(O) Pyridinyl Z₁: CHF₂ (meta)S Pyrazinyl NH—C(O) Pyridinyl Z₁: CHF₂ (ortho) S Pyrazinyl NH—C(O)Pyridinyl Z₁: CF₃ (para) S Pyrazinyl NH—C(O) Pyridinyl Z₁: CF₃ (meta) SPyrazinyl NH—C(O) Pyridinyl Z₁: CF₃ (ortho) S Pyrazinyl NH—C(O)Pyridinyl Z₁: CH₂—CH₂F (para) S Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₂F(meta) S Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₂—CH₂F (ortho) S PyrazinylNH—C(O) Pyridinyl Z₁: CH₂—CHF₂ (para) S Pyrazinyl NH—C(O) Pyridinyl Z₁:CH₂—CHF₂ (meta) S Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₂—CHF₂ (ortho) SPyrazinyl NH—C(O) Pyridinyl Z₁: CH₂—CF₃ (para) S Pyrazinyl NH—C(O)Pyridinyl Z₁: CH₂—CF₃ (meta) S Pyrazinyl NH—C(O) Pyridinyl Z₁: CH₂—CF₃(ortho) S Pyrazinyl NH—C(O) Pyrimidinyl None S Pyrazinyl NH—C(O)Pyrimidinyl Z₁: F (para) S Pyrazinyl NH—C(O) Pyrimidinyl Z₁: F (meta) SPyrazinyl NH—C(O) Pyrimidinyl Z₁: F (ortho) S Pyrazinyl NH—C(O)Pyrimidinyl Z₁: F (para) Z₂: F (meta) S Pyrazinyl NH—C(O) PyrimidinylZ₁: Cl (meta) S Pyrazinyl NH—C(O) Pyrimidinyl Z₁: Cl (para) S PyrazinylNH—C(O) Pyrimidinyl Z₁: Cl (para) Z₂: Cl (meta) S Pyrazinyl NH—C(O)Pyrimidinyl Z₁: F (para) Z₂: Cl (meta) S Pyrazinyl NH—C(O) PyrimidinylZ₁: Cl (para) Z₂: F (meta) S Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₃(para) S Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₃ (meta) S PyrazinylNH—C(O) Pyrimidinyl Z₁: CH₃ (ortho) S Pyrazinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CH₃ (para) S Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CH₃ (meta) SPyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CH₃ (ortho) S Pyrazinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) S Pyrazinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (meta) S Pyrazinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CH₂—CH₃ or iPr (ortho) S Pyrazinyl NH—C(O)Pyrimidinyl Z₁: CH₂F (para) S Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₂F(meta) S Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₂F (ortho) S PyrazinylNH—C(O) Pyrimidinyl Z₁: CHF₂ (para) S Pyrazinyl NH—C(O) Pyrimidinyl Z₁:CHF₂ (meta) S Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CHF₂ (ortho) S PyrazinylNH—C(O) Pyrimidinyl Z₁: CF₃ (para) S Pyrazinyl NH—C(O) Pyrimidinyl Z₁:CF₃ (meta) S Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CF₃ (ortho) S PyrazinylNH—C(O) Pyrimidinyl Z₁: CH₂—CH₂F (para) S Pyrazinyl NH—C(O) PyrimidinylZ₁: CH₂—CH₂F (meta) S Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CH₂F (ortho)S Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CHF₂ (para) S Pyrazinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CHF₂ (meta) S Pyrazinyl NH—C(O) Pyrimidinyl Z₁:CH₂—CHF₂ (ortho) S Pyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CF₃ (para) SPyrazinyl NH—C(O) Pyrimidinyl Z₁: CH₂—CF₃ (meta) S Pyrazinyl NH—C(O)Pyrimidinyl Z₁: CH₂—CF₃ (ortho) S Pyrazinyl NH—C(O) Pyrazinyl None SPyrazinyl NH—C(O) Pyrazinyl Z₁: F (para) S Pyrazinyl NH—C(O) PyrazinylZ₁: F (meta) S Pyrazinyl NH—C(O) Pyrazinyl Z₁: F (ortho) S PyrazinylNH—C(O) Pyrazinyl Z₁: F (para) Z₂: F (meta) S Pyrazinyl NH—C(O)Pyrazinyl Z₁: Cl (meta) S Pyrazinyl NH—C(O) Pyrazinyl Z₁: Cl (para) SPyrazinyl NH—C(O) Pyrazinyl Z₁: Cl (para) Z₂: Cl (meta) S PyrazinylNH—C(O) Pyrazinyl Z₁: F (para) Z₂: Cl (meta) S Pyrazinyl NH—C(O)Pyrazinyl Z₁: Cl (para) Z₂: F (meta) S Pyrazinyl NH—C(O) Pyrazinyl Z₁:CH₃ (para) S Pyrazinyl NH—C(O) Pyrazinyl Z₁: CH₃ (meta) S PyrazinylNH—C(O) Pyrazinyl Z₁: CH₃ (ortho) S Pyrazinyl NH—C(O) Pyrazinyl Z₁:CH₂—CH₃ (para) S Pyrazinyl NH—C(O) Pyrazinyl Z₁: CH₂—CH₃ (meta) SPyrazinyl NH—C(O) Pyrazinyl Z₁: CH₂—CH₃ (ortho) S Pyrazinyl NH—C(O)Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) S Pyrazinyl NH—C(O) PyrazinylZ₁: CH₂—CH₂—CH₃ or iPr (meta) S Pyrazinyl NH—C(O) Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (ortho) S Pyrazinyl NH—C(O) Pyrazinyl Z₁: CH₂F (para)S Pyrazinyl NH—C(O) Pyrazinyl Z₁: CH₂F (meta) S Pyrazinyl NH—C(O)Pyrazinyl Z₁: CH₂F (ortho) S Pyrazinyl NH—C(O) Pyrazinyl Z₁: CHF₂ (para)S Pyrazinyl NH—C(O) Pyrazinyl Z₁: CHF₂ (meta) S Pyrazinyl NH—C(O)Pyrazinyl Z₁: CHF₂ (ortho) S Pyrazinyl NH—C(O) Pyrazinyl Z₁: CF₃ (para)S Pyrazinyl NH—C(O) Pyrazinyl Z₁: CF₃ (meta) S Pyrazinyl NH—C(O)Pyrazinyl Z₁: CF₃ (ortho) S Pyrazinyl NH—C(O) Pyrazinyl Z₁: CH₂—CH₂F(para) S Pyrazinyl NH—C(O) Pyrazinyl Z₁: CH₂—CH₂F (meta) S PyrazinylNH—C(O) Pyrazinyl Z₁: CH₂—CH₂F (ortho) S Pyrazinyl NH—C(O) Pyrazinyl Z₁:CH₂—CHF₂ (para) S Pyrazinyl NH—C(O) Pyrazinyl Z₁: CH₂—CHF₂ (meta) SPyrazinyl NH—C(O) Pyrazinyl Z₁: CH₂—CHF₂ (ortho) S Pyrazinyl NH—C(O)Pyrazinyl Z₁: CH₂—CF₃ (para) S Pyrazinyl NH—C(O) Pyrazinyl Z₁: CH₂—CF₃(meta) S Pyrazinyl NH—C(O) Pyrazinyl Z₁: CH₂—CF₃ (ortho) S PyrazinylNH—C(O) Pyrrolyl None S Pyrazinyl NH—C(O) Pyrrolyl Z₁: F (2) S PyrazinylNH—C(O) Pyrrolyl Z₁: F (3) S Pyrazinyl NH—C(O) Pyrrolyl Z₁: F (2) Z₂: F(3) S Pyrazinyl NH—C(O) Pyrrolyl Z₁: Cl (2) S Pyrazinyl NH—C(O) PyrrolylZ₁: Cl (3) S Pyrazinyl NH—C(O) Pyrrolyl Z₁: Cl (2) Z₂: Cl (3) SPyrazinyl NH—C(O) Pyrrolyl Z₁: F (2) Z₂: Cl (3) S Pyrazinyl NH—C(O)Pyrrolyl Z₁: Cl (2) Z₂: F (3) S Pyrazinyl NH—C(O) Pyrrolyl Z₁: CH₃ (2) SPyrazinyl NH—C(O) Pyrrolyl Z₁: CH₃ (3) S Pyrazinyl NH—C(O) Pyrrolyl Z₁:CH₂—CH₃ (2) S Pyrazinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₃ (3) S PyrazinylNH—C(O) Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) S Pyrazinyl NH—C(O) PyrrolylZ₁: CH₂—CH₂—CH₃ or iPr (3) S Pyrazinyl NH—C(O) Pyrrolyl Z₁: CH₂F (2) SPyrazinyl NH—C(O) Pyrrolyl Z₁: CH₂F (3) S Pyrazinyl NH—C(O) Pyrrolyl Z₁:CHF₂ (2) S Pyrazinyl NH—C(O) Pyrrolyl Z₁: CHF₂ (3) S Pyrazinyl NH—C(O)Pyrrolyl Z₁: CF₃ (2) S Pyrazinyl NH—C(O) Pyrrolyl Z₁: CF₃ (3) SPyrazinyl NH—C(O) Pyrrolyl Z₁: CH₂—CH₂F (2) S Pyrazinyl NH—C(O) PyrrolylZ₁: CH₂—CH₂F (3) S Pyrazinyl NH—C(O) Pyrrolyl Z₁: CH₂—CHF₂ (2) SPyrazinyl NH—C(O) Pyrrolyl Z₁: CH₂—CHF₂ (3) S Pyrazinyl NH—C(O) PyrrolylZ₁: CH₂—CF₃ (2) S Pyrazinyl NH—C(O) Pyrrolyl Z₁: CH₂—CF₃ (3) S PyrazinylNH—C(O) Imidazolyl None S Pyrazinyl NH—C(O) Imidazolyl Z₁: F (2) SPyrazinyl NH—C(O) Imidazolyl Z₁: F (3) S Pyrazinyl NH—C(O) ImidazolylZ₁: F (2) Z₂: F (3) S Pyrazinyl NH—C(O) Imidazolyl Z₁: Cl (2) SPyrazinyl NH—C(O) Imidazolyl Z₁: Cl (3) S Pyrazinyl NH—C(O) ImidazolylZ₁: Cl (2) Z₂: Cl (3) S Pyrazinyl NH—C(O) Imidazolyl Z₁: F (2) Z₂: Cl(3) S Pyrazinyl NH—C(O) Imidazolyl Z₁: Cl (2) Z₂: F (3) S PyrazinylNH—C(O) Imidazolyl Z₁: CH₃ (2) S Pyrazinyl NH—C(O) Imidazolyl Z₁: CH₃(3) S Pyrazinyl NH—C(O) Imidazolyl Z₁: CH₂—CH₃ (2) S Pyrazinyl NH—C(O)Imidazolyl Z₁: CH₂—CH₃ (3) S Pyrazinyl NH—C(O) Imidazolyl Z₁:CH₂—CH₂—CH₃ or iPr (2) S Pyrazinyl NH—C(O) Imidazolyl Z₁: CH₂—CH₂—CH₃ oriPr (3) S Pyrazinyl NH—C(O) Imidazolyl Z₁: CH₂F (2) S Pyrazinyl NH—C(O)Imidazolyl Z₁: CH₂F (3) S Pyrazinyl NH—C(O) Imidazolyl Z₁: CHF₂ (2) SPyrazinyl NH—C(O) Imidazolyl Z₁: CHF₂ (3) S Pyrazinyl NH—C(O) ImidazolylZ₁: CF₃ (2) S Pyrazinyl NH—C(O) Imidazolyl Z₁: CF₃ (3) S PyrazinylNH—C(O) Imidazolyl Z₁: CH₂—CH₂F (2) S Pyrazinyl NH—C(O) Imidazolyl Z₁:CH₂—CH₂F (3) S Pyrazinyl NH—C(O) Imidazolyl Z₁: CH₂—CHF₂ (2) S PyrazinylNH—C(O) Imidazolyl Z₁: CH₂—CHF₂ (3) S Pyrazinyl NH—C(O) Imidazolyl Z₁:CH₂—CF₃ (2) S Pyrazinyl NH—C(O) Imidazolyl Z₁: CH₂—CF₃ (3) S PyrazinylNH—C(O) Furanyl None S Pyrazinyl NH—C(O) Furanyl Z₁: F (2) S PyrazinylNH—C(O) Furanyl Z₁: F (3) S Pyrazinyl NH—C(O) Furanyl Z₁: F (2) Z₂: F(3) S Pyrazinyl NH—C(O) Furanyl Z₁: Cl (2) S Pyrazinyl NH—C(O) FuranylZ₁: Cl (3) S Pyrazinyl NH—C(O) Furanyl Z₁: Cl (2) Z₂: Cl (3) S PyrazinylNH—C(O) Furanyl Z₁: F (2) Z₂: Cl (3) S Pyrazinyl NH—C(O) Furanyl Z₁: Cl(2) Z₂: F (3) S Pyrazinyl NH—C(O) Furanyl Z₁: CH₃ (2) S PyrazinylNH—C(O) Furanyl Z₁: CH₃ (3) S Pyrazinyl NH—C(O) Furanyl Z₁: CH₂—CH₃ (2)S Pyrazinyl NH—C(O) Furanyl Z₁: CH₂—CH₃ (3) S Pyrazinyl NH—C(O) FuranylZ₁: CH₂—CH₂—CH₃ or iPr (2) S Pyrazinyl NH—C(O) Furanyl Z₁: CH₂—CH₂—CH₃or iPr (3) S Pyrazinyl NH—C(O) Furanyl Z₁: CH₂F (2) S Pyrazinyl NH—C(O)Furanyl Z₁: CH₂F (3) S Pyrazinyl NH—C(O) Furanyl Z₁: CHF₂ (2) SPyrazinyl NH—C(O) Furanyl Z₁: CHF₂ (3) S Pyrazinyl NH—C(O) Furanyl Z₁:CF₃ (2) S Pyrazinyl NH—C(O) Furanyl Z₁: CF₃ (3) S Pyrazinyl NH—C(O)Furanyl Z₁: CH₂—CH₂F (2) S Pyrazinyl NH—C(O) Furanyl Z₁: CH₂—CH₂F (3) SPyrazinyl NH—C(O) Furanyl Z₁: CH₂—CHF₂ (2) S Pyrazinyl NH—C(O) FuranylZ₁: CH₂—CHF₂ (3) S Pyrazinyl NH—C(O) Furanyl Z₁: CH₂—CF₃ (2) S PyrazinylNH—C(O) Furanyl Z₁: CH₂—CF₃ (3) S Pyrazinyl NH—C(O) Oxazolyl None SPyrazinyl NH—C(O) Oxazolyl Z₁: F (2) S Pyrazinyl NH—C(O) Oxazolyl Z₁: F(3) S Pyrazinyl NH—C(O) Oxazolyl Z₁: F (2) Z₂: F (3) S Pyrazinyl NH—C(O)Oxazolyl Z₁: Cl (2) S Pyrazinyl NH—C(O) Oxazolyl Z₁: Cl (3) S PyrazinylNH—C(O) Oxazolyl Z₁: Cl (2) Z₂: Cl (3) S Pyrazinyl NH—C(O) Oxazolyl Z₁:F (2) Z₂: Cl (3) S Pyrazinyl NH—C(O) Oxazolyl Z₁: Cl (2) Z₂: F (3) SPyrazinyl NH—C(O) Oxazolyl Z₁: CH₃ (2) S Pyrazinyl NH—C(O) Oxazolyl Z₁:CH₃ (3) S Pyrazinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₃ (2) S Pyrazinyl NH—C(O)Oxazolyl Z₁: CH₂—CH₃ (3) S Pyrazinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₂—CH₃ oriPr (2) S Pyrazinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) SPyrazinyl NH—C(O) Oxazolyl Z₁: CH₂F (2) S Pyrazinyl NH—C(O) Oxazolyl Z₁:CH₂F (3) S Pyrazinyl NH—C(O) Oxazolyl Z₁: CHF₂ (2) S Pyrazinyl NH—C(O)Oxazolyl Z₁: CHF₂ (3) S Pyrazinyl NH—C(O) Oxazolyl Z₁: CF₃ (2) SPyrazinyl NH—C(O) Oxazolyl Z₁: CF₃ (3) S Pyrazinyl NH—C(O) Oxazolyl Z₁:CH₂—CH₂F (2) S Pyrazinyl NH—C(O) Oxazolyl Z₁: CH₂—CH₂F (3) S PyrazinylNH—C(O) Oxazolyl Z₁: CH₂—CHF₂ (2) S Pyrazinyl NH—C(O) Oxazolyl Z₁:CH₂—CHF₂ (3) S Pyrazinyl NH—C(O) Oxazolyl Z₁: CH₂—CF₃ (2) S PyrazinylNH—C(O) Oxazolyl Z₁: CH₂—CF₃ (3) S Pyrazinyl NH—C(O) Thiophenyl None SPyrazinyl NH—C(O) Thiophenyl Z₁: F (2) S Pyrazinyl NH—C(O) ThiophenylZ₁: F (3) S Pyrazinyl NH—C(O) Thiophenyl Z₁: F (2) Z₂: F (3) S PyrazinylNH—C(O) Thiophenyl Z₁: Cl (2) S Pyrazinyl NH—C(O) Thiophenyl Z₁: Cl (3)S Pyrazinyl NH—C(O) Thiophenyl Z₁: Cl (2) Z₂: Cl (3) S Pyrazinyl NH—C(O)Thiophenyl Z₁: F (2) Z₂: Cl (3) S Pyrazinyl NH—C(O) Thiophenyl Z₁: Cl(2) Z₂: F (3) S Pyrazinyl NH—C(O) Thiophenyl Z₁: CH₃ (2) S PyrazinylNH—C(O) Thiophenyl Z₁: CH₃ (3) S Pyrazinyl NH—C(O) Thiophenyl Z₁:CH₂—CH₃ (2) S Pyrazinyl NH—C(O) Thiophenyl Z₁: CH₂—CH₃ (3) S PyrazinylNH—C(O) Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (2) S Pyrazinyl NH—C(O)Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (3) S Pyrazinyl NH—C(O) Thiophenyl Z₁:CH₂F (2) S Pyrazinyl NH—C(O) Thiophenyl Z₁: CH₂F (3) S Pyrazinyl NH—C(O)Thiophenyl Z₁: CHF₂ (2) S Pyrazinyl NH—C(O) Thiophenyl Z₁: CHF₂ (3) SPyrazinyl NH—C(O) Thiophenyl Z₁: CF₃ (2) S Pyrazinyl NH—C(O) ThiophenylZ₁: CF₃ (3) S Pyrazinyl NH—C(O) Thiophenyl Z₁: CH₂—CH₂F (2) S PyrazinylNH—C(O) Thiophenyl Z₁: CH₂—CH₂F (3) S Pyrazinyl NH—C(O) Thiophenyl Z₁:CH₂—CHF₂ (2) S Pyrazinyl NH—C(O) Thiophenyl Z₁: CH₂—CHF₂ (3) S PyrazinylNH—C(O) Thiophenyl Z₁: CH₂—CF₃ (2) S Pyrazinyl NH—C(O) Thiophenyl Z₁:CH₂—CF₃ (3) S Pyrazinyl NH—C(O) Thiazolyl None S Pyrazinyl NH—C(O)Thiazolyl Z₁: F (2) S Pyrazinyl NH—C(O) Thiazolyl Z₁: F (3) S PyrazinylNH—C(O) Thiazolyl Z₁: F (2) Z₂: F (3) S Pyrazinyl NH—C(O) Thiazolyl Z₁:Cl (2) S Pyrazinyl NH—C(O) Thiazolyl Z₁: Cl (3) S Pyrazinyl NH—C(O)Thiazolyl Z₁: Cl (2) Z₂: Cl (3) S Pyrazinyl NH—C(O) Thiazolyl Z₁: F (2)Z₂: Cl (3) S Pyrazinyl NH—C(O) Thiazolyl Z₁: Cl (2) Z₂: F (3) SPyrazinyl NH—C(O) Thiazolyl Z₁: CH₃ (2) S Pyrazinyl NH—C(O) ThiazolylZ₁: CH₃ (3) S Pyrazinyl NH—C(O) Thiazolyl Z₁: CH₂—CH₃ (2) S PyrazinylNH—C(O) Thiazolyl Z₁: CH₂—CH₃ (3) S Pyrazinyl NH—C(O) Thiazolyl Z₁:CH₂—CH₂—CH₃ or iPr (2) S Pyrazinyl NH—C(O) Thiazolyl Z₁: CH₂—CH₂—CH₃ oriPr (3) S Pyrazinyl NH—C(O) Thiazolyl Z₁: CH₂F (2) S Pyrazinyl NH—C(O)Thiazolyl Z₁: CH₂F (3) S Pyrazinyl NH—C(O) Thiazolyl Z₁: CHF₂ (2) SPyrazinyl NH—C(O) Thiazolyl Z₁: CHF₂ (3) S Pyrazinyl NH—C(O) ThiazolylZ₁: CF₃ (2) S Pyrazinyl NH—C(O) Thiazolyl Z₁: CF₃ (3) S PyrazinylNH—C(O) Thiazolyl Z₁: CH₂—CH₂F (2) S Pyrazinyl NH—C(O) Thiazolyl Z₁:CH₂—CH₂F (3) S Pyrazinyl NH—C(O) Thiazolyl Z₁: CH₂—CHF₂ (2) S PyrazinylNH—C(O) Thiazolyl Z₁: CH₂—CHF₂ (3) S Pyrazinyl NH—C(O) Thiazolyl Z₁:CH₂—CF₃ (2) S Pyrazinyl NH—C(O) Thiazolyl Z₁: CH₂—CF₃ (3) S PyrazinylNH—SO₂ Phenyl None S Pyrazinyl NH—SO₂ Phenyl Z₁: F (para) S PyrazinylNH—SO₂ phenyl Z₁: F (meta) S Pyrazinyl NH—SO₂ phenyl Z₁: F (ortho) SPyrazinyl NH—SO₂ phenyl Z₁: F (para) Z₂: F (meta) S Pyrazinyl NH—SO₂Phenyl Z₁: Cl (meta) S Pyrazinyl NH—SO₂ Phenyl Z₁: Cl (para) S PyrazinylNH—SO₂ Phenyl Z₁: Cl (para) Z₂: Cl (meta) S Pyrazinyl NH—SO₂ Phenyl Z₁:F (para) Z₁: Cl (meta) S Pyrazinyl NH—SO₂ Phenyl Z₁: Cl (para) Z₂: F(meta) S Pyrazinyl NH—SO₂ Phenyl Z₁: CH₃ (para) S Pyrazinyl NH—SO₂Phenyl Z₁: CH₃ (meta) S Pyrazinyl NH—SO₂ Phenyl Z₁: CH₃ (ortho) SPyrazinyl NH—SO₂ Phenyl Z₁: CH₂—CH₃ (para) S Pyrazinyl NH—SO₂ Phenyl Z₁:CH₂—CH₃ (meta) S Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂—CH₃ (ortho) S PyrazinylNH—SO₂ Phenyl Z₁: CH₂—CH₂—CH₃ or iPr (para) S Pyrazinyl NH—SO₂ PhenylZ₁: CH₂—CH₂—CH₃ or iPr (meta) S Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂—CH₃or iPr (ortho) S Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂F (para) S PyrazinylNH—SO₂ Phenyl Z₁: CH₂F (meta) S Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂F (ortho)S Pyrazinyl NH—SO₂ Phenyl Z₁: CHF₂ (para) S Pyrazinyl NH—SO₂ Phenyl Z₁:CHF₂ (meta) S Pyrazinyl NH—SO₂ Phenyl Z₁: CHF₂ (ortho) S PyrazinylNH—SO₂ Phenyl Z₁: CF₃ (para) S Pyrazinyl NH—SO₂ Phenyl Z₁: CF₃ (meta) SPyrazinyl NH—SO₂ Phenyl Z₁: CF₃ (ortho) S Pyrazinyl NH—SO₂ Phenyl Z₁:CH₂—CH₂F (para) S Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂F (meta) SPyrazinyl NH—SO₂ Phenyl Z₁: CH₂—CH₂F (ortho) S Pyrazinyl NH—SO₂ PhenylZ₁: CH₂—CHF₂ (para) S Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂—CHF₂ (meta) SPyrazinyl NH—SO₂ Phenyl Z₁: CH₂—CHF₂ (ortho) S Pyrazinyl NH—SO₂ PhenylZ₁: CH₂—CF₃ (para) S Pyrazinyl NH—SO₂ Phenyl Z₁: CH₂—CF₃ (meta) SPyrazinyl NH—SO₂ Phenyl Z₁: CH₂—CF₃ (ortho) S Pyrazinyl NH—SO₂ PyridinylNone S Pyrazinyl NH—SO₂ Pyridinyl Z₁: F (para) S Pyrazinyl NH—SO₂Pyridinyl Z₁: F (meta) S Pyrazinyl NH—SO₂ Pyridinyl Z₁: F (ortho) SPyrazinyl NH—SO₂ Pyridinyl Z₁: F (para) Z₂: F (meta) S Pyrazinyl NH—SO₂Pyridinyl Z₁: Cl (meta) S Pyrazinyl NH—SO₂ Pyridinyl Z₁: Cl (para) SPyrazinyl NH—SO₂ Pyridinyl Z₁: Cl (para) Z₂: Cl (meta) S PyrazinylNH—SO₂ Pyridinyl Z₁: F (para) Z₂: Cl (meta) S Pyrazinyl NH—SO₂ PyridinylZ₁: Cl (para) Z₂: F (meta) S Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₃ (para) SPyrazinyl NH—SO₂ Pyridinyl Z₁: CH₃ (meta) S Pyrazinyl NH—SO₂ PyridinylZ₁: CH₃ (ortho) S Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₃ (para) SPyrazinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₃ (meta) S Pyrazinyl NH—SO₂Pyridinyl Z₁: CH₂—CH₃ (ortho) S Pyrazinyl NH—SO₂ Pyridinyl Z₁:CH₂—CH₂—CH₃ or iPr (para) S Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₂—CH₃or iPr (meta) S Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₂—CH₃ or iPr(ortho) S Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₂F (para) S Pyrazinyl NH—SO₂Pyridinyl Z₁: CH₂F (meta) S Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₂F (ortho)S Pyrazinyl NH—SO₂ Pyridinyl Z₁: CHF₂ (para) S Pyrazinyl NH—SO₂Pyridinyl Z₁: CHF₂ (meta) S Pyrazinyl NH—SO₂ Pyridinyl Z₁: CHF₂ (ortho)S Pyrazinyl NH—SO₂ Pyridinyl Z₁: CF₃ (para) S Pyrazinyl NH—SO₂ PyridinylZ₁: CF₃ (meta) S Pyrazinyl NH—SO₂ Pyridinyl Z₁: CF₃ (ortho) S PyrazinylNH—SO₂ Pyridinyl Z₁: CH₂—CH₂F (para) S Pyrazinyl NH—SO₂ Pyridinyl Z₁:CH₂—CH₂F (meta) S Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₂—CH₂F (ortho) SPyrazinyl NH—SO₂ Pyridinyl Z₁: CH₂—CHF₂ (para) S Pyrazinyl NH—SO₂Pyridinyl Z₁: CH₂—CHF₂ (meta) S Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₂—CHF₂(ortho) S Pyrazinyl NH—SO₂ Pyridinyl Z₁: CH₂—CF₃ (para) S PyrazinylNH—SO₂ Pyridinyl Z₁: CH₂—CF₃ (meta) S Pyrazinyl NH—SO₂ Pyridinyl Z₁:CH₂—CF₃ (ortho) S Pyrazinyl NH—SO₂ Pyrimidinyl None S Pyrazinyl NH—SO₂Pyrimidinyl Z₁: F (para) S Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: F (meta) SPyrazinyl NH—SO₂ Pyrimidinyl Z₁: F (ortho) S Pyrazinyl NH—SO₂Pyrimidinyl Z₁: F (para) Z₂: F (meta) S Pyrazinyl NH—SO₂ Pyrimidinyl Z₁:Cl (meta) S Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: Cl (para) S PyrazinylNH—SO₂ Pyrimidinyl Z₁: Cl (para) Z₂: Cl (meta) S Pyrazinyl NH—SO₂Pyrimidinyl Z₁: F (para) Z₂: Cl (meta) S Pyrazinyl NH—SO₂ PyrimidinylZ₁: Cl (para) Z₂: F (meta) S Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₃ (para)S Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₃ (meta) S Pyrazinyl NH—SO₂Pyrimidinyl Z₁: CH₃ (ortho) S Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₃(para) S Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₃ (meta) S PyrazinylNH—SO₂ Pyrimidinyl Z₁: CH₂—CH₃ (ortho) S Pyrazinyl NH—SO₂ PyrimidinylZ₁: CH₂—CH₂—CH₃ or iPr (para) S Pyrazinyl NH—SO₂ Pyrimidinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) S Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂—CH₃or iPr (ortho) S Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₂F (para) SPyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₂F (meta) S Pyrazinyl NH—SO₂Pyrimidinyl Z₁: CH₂F (ortho) S Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CHF₂(para) S Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CHF₂ (meta) S Pyrazinyl NH—SO₂Pyrimidinyl Z₁: CHF₂ (ortho) S Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CF₃(para) S Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CF₃ (meta) S Pyrazinyl NH—SO₂Pyrimidinyl Z₁: CF₃ (ortho) S Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂F(para) S Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂F (meta) S PyrazinylNH—SO₂ Pyrimidinyl Z₁: CH₂—CH₂F (ortho) S Pyrazinyl NH—SO₂ PyrimidinylZ₁: CH₂—CHF₂ (para) S Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CHF₂ (meta) SPyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CHF₂ (ortho) S Pyrazinyl NH—SO₂Pyrimidinyl Z₁: CH₂—CF₃ (para) S Pyrazinyl NH—SO₂ Pyrimidinyl Z₁:CH₂—CF₃ (meta) S Pyrazinyl NH—SO₂ Pyrimidinyl Z₁: CH₂—CF₃ (ortho) SPyrazinyl NH—SO₂ Pyrazinyl None S Pyrazinyl NH—SO₂ Pyrazinyl Z₁: F(para) S Pyrazinyl NH—SO₂ Pyrazinyl Z₁: F (meta) S Pyrazinyl NH—SO₂Pyrazinyl Z₁: F (ortho) S Pyrazinyl NH—SO₂ Pyrazinyl Z₁: F (para) Z₂: F(meta) S Pyrazinyl NH—SO₂ Pyrazinyl Z₁: Cl (meta) S Pyrazinyl NH—SO₂Pyrazinyl Z₁: Cl (para) S Pyrazinyl NH—SO₂ Pyrazinyl Z₁: Cl (para) Z₂:Cl (meta) S Pyrazinyl NH—SO₂ Pyrazinyl Z₁: F (para) Z₂: Cl (meta) SPyrazinyl NH—SO₂ Pyrazinyl Z₁: Cl (para) Z₂: F (meta) S Pyrazinyl NH—SO₂Pyrazinyl Z₁: CH₃ (para) S Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₃ (meta) SPyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₃ (ortho) S Pyrazinyl NH—SO₂ PyrazinylZ₁: CH₂—CH₃ (para) S Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₃ (meta) SPyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₃ (ortho) S Pyrazinyl NH—SO₂Pyrazinyl Z₁: CH₂—CH₂—CH₃ or iPr (para) S Pyrazinyl NH—SO₂ Pyrazinyl Z₁:CH₂—CH₂—CH₃ or iPr (meta) S Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₂—CH₃or iPr (ortho) S Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₂F (para) S PyrazinylNH—SO₂ Pyrazinyl Z₁: CH₂F (meta) S Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₂F(ortho) S Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CHF₂ (para) S Pyrazinyl NH—SO₂Pyrazinyl Z₁: CHF₂ (meta) S Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CHF₂ (ortho)S Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CF₃ (para) S Pyrazinyl NH—SO₂ PyrazinylZ₁: CF₃ (meta) S Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CF₃ (ortho) S PyrazinylNH—SO₂ Pyrazinyl Z₁: CH₂—CH₂F (para) S Pyrazinyl NH—SO₂ Pyrazinyl Z₁:CH₂—CH₂F (meta) S Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CH₂F (ortho) SPyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CHF₂ (para) S Pyrazinyl NH—SO₂Pyrazinyl Z₁: CH₂—CHF₂ (meta) S Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CHF₂(ortho) S Pyrazinyl NH—SO₂ Pyrazinyl Z₁: CH₂—CF₃ (para) S PyrazinylNH—SO₂ Pyrazinyl Z₁: CH₂—CF₃ (meta) S Pyrazinyl NH—SO₂ Pyrazinyl Z₁:CH₂—CF₃ (ortho) S Pyrazinyl NH—SO₂ Pyrrolyl None S Pyrazinyl NH—SO₂Pyrrolyl Z₁: F (2) S Pyrazinyl NH—SO₂ Pyrrolyl Z₁: F (3) S PyrazinylNH—SO₂ Pyrrolyl Z₁: F (2) Z₂: F (3) S Pyrazinyl NH—SO₂ Pyrrolyl Z₁: Cl(2) S Pyrazinyl NH—SO₂ Pyrrolyl Z₁: Cl (3) S Pyrazinyl NH—SO₂ PyrrolylZ₁: Cl (2) Z₂: Cl (3) S Pyrazinyl NH—SO₂ Pyrrolyl Z₁: F (2) Z₂: Cl (3) SPyrazinyl NH—SO₂ Pyrrolyl Z₁: Cl (2) Z₂: F (3) S Pyrazinyl NH—SO₂Pyrrolyl Z₁: CH₃ (2) S Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CH₃ (3) S PyrazinylNH—SO₂ Pyrrolyl Z₁: CH₂—CH₃ (2) S Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CH₃(3) S Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) S PyrazinylNH—SO₂ Pyrrolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) S Pyrazinyl NH—SO₂ PyrrolylZ₁: CH₂F (2) S Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CH₂F (3) S Pyrazinyl NH—SO₂Pyrrolyl Z₁: CHF₂ (2) S Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CHF₂ (3) SPyrazinyl NH—SO₂ Pyrrolyl Z₁: CF₃ (2) S Pyrazinyl NH—SO₂ Pyrrolyl Z₁:CF₃ (3) S Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CH₂F (2) S Pyrazinyl NH—SO₂Pyrrolyl Z₁: CH₂—CH₂F (3) S Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CHF₂ (2) SPyrazinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CHF₂ (3) S Pyrazinyl NH—SO₂ PyrrolylZ₁: CH₂—CF₃ (2) S Pyrazinyl NH—SO₂ Pyrrolyl Z₁: CH₂—CF₃ (3) S PyrazinylNH—SO₂ Imidazolyl None S Pyrazinyl NH—SO₂ Imidazolyl Z₁: F (2) SPyrazinyl NH—SO₂ Imidazolyl Z₁: F (3) S Pyrazinyl NH—SO₂ Imidazolyl Z₁:F (2) Z₂: F (3) S Pyrazinyl NH—SO₂ Imidazolyl Z₁: Cl (2) S PyrazinylNH—SO₂ Imidazolyl Z₁: Cl (3) S Pyrazinyl NH—SO₂ Imidazolyl Z₁: Cl (2)Z₂: Cl (3) S Pyrazinyl NH—SO₂ Imidazolyl Z₁: F (2) Z₂: Cl (3) SPyrazinyl NH—SO₂ Imidazolyl Z₁: Cl (2) Z₂: F (3) S Pyrazinyl NH—SO₂Imidazolyl Z₁: CH₃ (2) S Pyrazinyl NH—SO₂ Imidazolyl Z₁: CH₃ (3) SPyrazinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₃ (2) S Pyrazinyl NH—SO₂Imidazolyl Z₁: CH₂—CH₃ (3) S Pyrazinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₂—CH₃or iPr (2) S Pyrazinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) SPyrazinyl NH—SO₂ Imidazolyl Z₁: CH₂F (2) S Pyrazinyl NH—SO₂ ImidazolylZ₁: CH₂F (3) S Pyrazinyl NH—SO₂ Imidazolyl Z₁: CHF₂ (2) S PyrazinylNH—SO₂ Imidazolyl Z₁: CHF₂ (3) S Pyrazinyl NH—SO₂ Imidazolyl Z₁: CF₃ (2)S Pyrazinyl NH—SO₂ Imidazolyl Z₁: CF₃ (3) S Pyrazinyl NH—SO₂ ImidazolylZ₁: CH₂—CH₂F (2) S Pyrazinyl NH—SO₂ Imidazolyl Z₁: CH₂—CH₂F (3) SPyrazinyl NH—SO₂ Imidazolyl Z₁: CH₂—CHF₂ (2) S Pyrazinyl NH—SO₂Imidazolyl Z₁: CH₂—CHF₂ (3) S Pyrazinyl NH—SO₂ Imidazolyl Z₁: CH₂—CF₃(2) S Pyrazinyl NH—SO₂ Imidazolyl Z₁: CH₂—CF₃ (3) S Pyrazinyl NH—SO₂Furanyl None S Pyrazinyl NH—SO₂ Furanyl Z₁: F (2) S Pyrazinyl NH—SO₂Furanyl Z₁: F (3) S Pyrazinyl NH—SO₂ Furanyl Z₁: F (2) Z₂: F (3) SPyrazinyl NH—SO₂ Furanyl Z₁: Cl (2) S Pyrazinyl NH—SO₂ Furanyl Z₁: Cl(3) S Pyrazinyl NH—SO₂ Furanyl Z₁: Cl (2) Z₂: Cl (3) S Pyrazinyl NH—SO₂Furanyl Z₁: F (2) Z₂: Cl (3) S Pyrazinyl NH—SO₂ Furanyl Z₁: Cl (2) Z₂: F(3) S Pyrazinyl NH—SO₂ Furanyl Z₁: CH₃ (2) S Pyrazinyl NH—SO₂ FuranylZ₁: CH₃ (3) S Pyrazinyl NH—SO₂ Furanyl Z₁: CH₂—CH₃ (2) S PyrazinylNH—SO₂ Furanyl Z₁: CH₂—CH₃ (3) S Pyrazinyl NH—SO₂ Furanyl Z₁:CH₂—CH₂—CH₃ or iPr (2) S Pyrazinyl NH—SO₂ Furanyl Z₁: CH₂—CH₂—CH₃ or iPr(3) S Pyrazinyl NH—SO₂ Furanyl Z₁: CH₂F (2) S Pyrazinyl NH—SO₂ FuranylZ₁: CH₂F (3) S Pyrazinyl NH—SO₂ Furanyl Z₁: CHF₂ (2) S Pyrazinyl NH—SO₂Furanyl Z₁: CHF₂ (3) S Pyrazinyl NH—SO₂ Furanyl Z₁: CF₃ (2) S PyrazinylNH—SO₂ Furanyl Z₁: CF₃ (3) S Pyrazinyl NH—SO₂ Furanyl Z₁: CH₂—CH₂F (2) SPyrazinyl NH—SO₂ Furanyl Z₁: CH₂—CH₂F (3) S Pyrazinyl NH—SO₂ Furanyl Z₁:CH₂—CHF₂ (2) S Pyrazinyl NH—SO₂ Furanyl Z₁: CH₂—CHF₂ (3) S PyrazinylNH—SO₂ Furanyl Z₁: CH₂—CF₃ (2) S Pyrazinyl NH—SO₂ Furanyl Z₁: CH₂—CF₃(3) S Pyrazinyl NH—SO₂ Oxazolyl None S Pyrazinyl NH—SO₂ Oxazolyl Z₁: F(2) S Pyrazinyl NH—SO₂ Oxazolyl Z₁: F (3) S Pyrazinyl NH—SO₂ OxazolylZ₁: F (2) Z₂: F (3) S Pyrazinyl NH—SO₂ Oxazolyl Z₁: Cl (2) S PyrazinylNH—SO₂ Oxazolyl Z₁: Cl (3) S Pyrazinyl NH—SO₂ Oxazolyl Z₁: Cl (2) Z₂: Cl(3) S Pyrazinyl NH—SO₂ Oxazolyl Z₁: F (2) Z₂: Cl (3) S Pyrazinyl NH—SO₂Oxazolyl Z₁: Cl (2) Z₁: F (3) S Pyrazinyl NH—SO₂ Oxazolyl Z₁: CH₃ (2) SPyrazinyl NH—SO₂ Oxazolyl Z₁: CH₃ (3) S Pyrazinyl NH—SO₂ Oxazolyl Z₁:CH₂—CH₃ (2) S Pyrazinyl NH—SO₂ Oxazolyl Z₁: CH₂—CH₃ (3) S PyrazinylNH—SO₂ Oxazolyl Z₁: CH₂—CH₂—CH₃ or iPr (2) S Pyrazinyl NH—SO₂ OxazolylZ₁: CH₂—CH₂—CH₃ or iPr (3) S Pyrazinyl NH—SO₂ Oxazolyl Z₁: CH₂F (2) SPyrazinyl NH—SO₂ Oxazolyl Z₁: CH₂F (3) S Pyrazinyl NH—SO₂ Oxazolyl Z₁:CHF₂ (2) S Pyrazinyl NH—SO₂ Oxazolyl Z₁: CHF₂ (3) S Pyrazinyl NH—SO₂Oxazolyl Z₁: CF₃ (2) S Pyrazinyl NH—SO₂ Oxazolyl Z₁: CF₃ (3) S PyrazinylNH—SO₂ Oxazolyl Z₁: CH₂—CH₂F (2) S Pyrazinyl NH—SO₂ Oxazolyl Z₁:CH₂—CH₂F (3) S Pyrazinyl NH—SO₂ Oxazolyl Z₁: CH₂—CHF₂ (2) S PyrazinylNH—SO₂ Oxazolyl Z₁: CH₂—CHF₂ (3) S Pyrazinyl NH—SO₂ Oxazolyl Z₁: CH₂—CF₃(2) S Pyrazinyl NH—SO₂ Oxazolyl Z₁: CH₂—CF₃ (3) S Pyrazinyl NH—SO₂Thiophenyl None S Pyrazinyl NH—SO₂ Thiophenyl Z₁: F (2) S PyrazinylNH—SO₂ Thiophenyl Z₁: F (3) S Pyrazinyl NH—SO₂ Thiophenyl Z₁: F (2) Z₂:F (3) S Pyrazinyl NH—SO₂ Thiophenyl Z₁: Cl (2) S Pyrazinyl NH—SO₂Thiophenyl Z₁: Cl (3) S Pyrazinyl NH—SO₂ Thiophenyl Z₁: Cl (2) Z₂: Cl(3) S Pyrazinyl NH—SO₂ Thiophenyl Z₁: F (2) Z₂: Cl (3) S PyrazinylNH—SO₂ Thiophenyl Z₁: Cl (2) Z₂: F (3) S Pyrazinyl NH—SO₂ Thiophenyl Z₁:CH₃ (2) S Pyrazinyl NH—SO₂ Thiophenyl Z₁: CH₃ (3) S Pyrazinyl NH—SO₂Thiophenyl Z₁: CH₂—CH₃ (2) S Pyrazinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₃ (3)S Pyrazinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (2) S PyrazinylNH—SO₂ Thiophenyl Z₁: CH₂—CH₂—CH₃ or iPr (3) S Pyrazinyl NH—SO₂Thiophenyl Z₁: CH₂F (2) S Pyrazinyl NH—SO₂ Thiophenyl Z₁: CH₂F (3) SPyrazinyl NH—SO₂ Thiophenyl Z₁: CHF₂ (2) S Pyrazinyl NH—SO₂ ThiophenylZ₁: CHF₂ (3) S Pyrazinyl NH—SO₂ Thiophenyl Z₁: CF₃ (2) S PyrazinylNH—SO₂ Thiophenyl Z₁: CF₃ (3) S Pyrazinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₂F(2) S Pyrazinyl NH—SO₂ Thiophenyl Z₁: CH₂—CH₂F (3) S Pyrazinyl NH—SO₂Thiophenyl Z₁: CH₂—CHF₂ (2) S Pyrazinyl NH—SO₂ Thiophenyl Z₁: CH₂—CHF₂(3) S Pyrazinyl NH—SO₂ Thiophenyl Z₁: CH₂—CF₃ (2) S Pyrazinyl NH—SO₂Thiophenyl Z₁: CH₂—CF₃ (3) S Pyrazinyl NH—SO₂ Thiazolyl None S PyrazinylNH—SO₂ Thiazolyl Z₁: F (2) S Pyrazinyl NH—SO₂ Thiazolyl Z₁: F (3) SPyrazinyl NH—SO₂ Thiazolyl Z₁: F (2) Z₂: F (3) S Pyrazinyl NH—SO₂Thiazolyl Z₁: Cl (2) S Pyrazinyl NH—SO₂ Thiazolyl Z₁: Cl (3) S PyrazinylNH—SO₂ Thiazolyl Z₁: Cl (2) Z₂: Cl (3) S Pyrazinyl NH—SO₂ Thiazolyl Z₁:F (2) Z₂: Cl (3) S Pyrazinyl NH—SO₂ Thiazolyl Z₁: Cl (2) Z₂: F (3) SPyrazinyl NH—SO₂ Thiazolyl Z₁: CH₃ (2) S Pyrazinyl NH—SO₂ Thiazolyl Z₁:CH₃ (3) S Pyrazinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₃ (2) S Pyrazinyl NH—SO₂Thiazolyl Z₁: CH₂—CH₃ (3) S Pyrazinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₂—CH₃or iPr (2) S Pyrazinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₂—CH₃ or iPr (3) SPyrazinyl NH—SO₂ Thiazolyl Z₁: CH₂F (2) S Pyrazinyl NH—SO₂ Thiazolyl Z₁:CH₂F (3) S Pyrazinyl NH—SO₂ Thiazolyl Z₁: CHF₂ (2) S Pyrazinyl NH—SO₂Thiazolyl Z₁: CHF₂ (3) S Pyrazinyl NH—SO₂ Thiazolyl Z₁: CF₃ (2) SPyrazinyl NH—SO₂ Thiazolyl Z₁: CF₃ (3) S Pyrazinyl NH—SO₂ Thiazolyl Z₁:CH₂—CH₂F (2) S Pyrazinyl NH—SO₂ Thiazolyl Z₁: CH₂—CH₂F (3) S PyrazinylNH—SO₂ Thiazolyl Z₁: CH₂—CHF₂ (2) S Pyrazinyl NH—SO₂ Thiazolyl Z₁:CH₂—CHF₂ (3) S Pyrazinyl NH—SO₂ Thiazolyl Z₁: CH₂—CF₃ (2) S PyrazinylNH—SO₂ Thiazolyl Z₁: CH₂—CF₃ (3)

In Table 2, where C² is a 5-membered ring, the number in parenthesesfollowing the specification of the Z substituent indicates thesubstituent ring position, wherein the atom attached to L² is numbered1, and atoms are numbered consecutively around the ring, but excludingsubstitutions at those positions where linkage of the substitutent to aheteroatom is not chemically reasonable.

In Table 2, where C² is a 6-membered ring, substituent position isindicated relative to the attachment to L² using para, meta, and orthoterms in similar manner as for phenyl groups, but excludingsubstitutions at those positions where linkage of the substitutent to aheteroatom is not chemically reasonable.

Additional embodiments are also described with reference to thecompounds in Table 2. Each combination of L¹, C¹, L², and C² indicatedin Table 2 also specifies a narrow generic description of a group ofcompounds that can include different substituents on C² and/orsubstitutents on one or more of the moieties, L¹, C¹, and L². Preferablysuch substituents each include no more than 7 non-hydrogen atoms.

Likewise, additional embodiments of narrow generic compound descriptionsare provided in which for each combination of L¹, C¹, L², and C² thebi-cyclic core is also substituted at the 4-position, the 5-position, orboth the 4- and 5-positions with substituents as specified for FormulaI. In further embodiments, substitution at the 4- and/or 5-position iscombined with substituents as described in the preceding paragraph.

Exemplary Diseases Associated with c-Kit

The compounds described herein are useful for treating disorders relatedto c-Kit e.g., diseases related to improperly regulated kinase signaltransduction, including cell proliferative disorders, fibrotic disordersand metabolic disorders, among others. As described in more detail belowand in Lipson et al., U.S. 20040002534 (U.S. application Ser. No.10/600,868, filed Jun. 23, 2003) which is incorporated herein byreference in its entirety, cell proliferative disorders which can betreated by the present invention include cancers, and mast cellproliferative disorders.

The presence of c-kit has also been associated with a number ofdifferent types of cancers, as described below. In addition, theassociation between abnormalities in c-kit and disease are notrestricted to cancer. For example, as is also described in more detailbelow, c-kit has been associated with inflammatory diseases such asmastocytosis, asthmas, multiple sclerosis, inflammatory bowel syndromeand allergic rhinitis.

Exemplary Malignant Diseases Associated with c-Kit

Aberrant expression and/or activation of c-Kit has been implicated in avariety of cancers. Evidence for a contribution of c-Kit to neoplasticpathology includes its association with leukemias and mast cell tumors,small cell lung cancer, testicular cancer, and some cancers of thegastrointestinal tract and central nervous system. In addition, c-Kithas been implicated in playing a role in carcinogenesis of the femalegenital tract (Inoue, et al., 1994, Cancer Res. 54:3049-3053), sarcomasof neuroectodermal origin (Ricotti, et al., 1998, Blood 91:2397-2405),and Schwann cell neoplasia associated with neurofibromatosis (Ryan, etal., 1994, J. Neuro. Res. 37:415-432). It was found that mast cells areinvolved in modifying the tumor microenvironment and enhancing tumorgrowth (Yang et al., 2003, J Clin Invest. 112:1851-1861; Viskochil,2003, J Clin Invest. 112:1791-1793). Thus, c-Kit is a useful target intreating neurofibromatosis as well as malignant tumors.

Small cell lung carcinoma: c-Kit kinase receptor has been found to beaberrantly expressed in many cases of small cell lung carcinoma (SCLC)cells (Hibi, et al., 1991, Oncogene 6:2291-2296). Thus, as an example,inhibition of c-Kit kinase can be beneficial in treatment of SCLC, e.g.,to improve the long term survival of patients with SCLC.

Leukemias: SCF binding to the c-Kit protects hematopoietic stem andprogenitor cells from apoptosis (Lee, et al., 1997, J. Immunol.159:3211-3219), thereby contributing to colony formation andhematopoiesis. Expression of c-Kit is frequently observed in acutemyelocytic leukemia (AML), and in some cases of acute lymphocyticleukemia (ALL) (for reviews, see Sperling, et al., 1997, Haemat82:617-621; Escribano, et al., 1998, Leuk. Lymph. 30:459-466). Althoughc-Kit is expressed in the majority of AML cells, its expression does notappear to be prognostic of disease progression (Sperling, et al, 1997,Haemat 82:617-621). However, SCF protected AML cells from apoptosisinduced by chemotherapeutic agents (Hassan, et al., 1996, Acta. Hem.95:257-262). Inhibition of c-Kit by the present invention will enhancethe efficacy of these agents and can induce apoptosis of AML cells.

The clonal growth of cells from patients with myelodysplastic syndrome(Sawada, et al., Blood 1996, 88:319-327) or chronic myelogenous leukemia(CML) (Sawai, et al., Exp. Hem. 1996, 2:116-122) was found to besignificantly enhanced by SCF in combination with other cytokines. CMLis characterized by expansion of Philadelphia chromosome positive cellsof the marrow (Verfullie, et al., Leuk. 1998, 12:136-138), which appearsto primarily result from inhibition of apoptotic death (Jones, Curr.Opin. One. 1997, 9:3-7). The product of the Philadelphia chromosome,p210^(BCR-ABL), has been reported to mediate inhibition of apoptosis(Bedi, et al., Blood 1995, 86:1148-1158). Since p210^(BCR-ABL) and thec-Kit RTK both inhibit apoptosis and p62^(dok) has been suggested as asubstrate (Carpino, et al., Cell 1997, 88:197-204), clonal expansionmediated by these kinases may occur through a common signaling pathway.However, c-Kit has also been reported to interact directly withp210^(BCR-ABL) (Hallek, et al., Brit. J Haem. 1996, 94:5-16), whichsuggests that c-Kit has a more causative role in CML pathology.Therefore, inhibition of c-Kit kinase will be useful in the treatment ofthe above disorders.

Gastrointestinal cancers: Normal colorectal mucosa does not expressc-Kit (Bellone, et al., 1997, J. Cell Physiol. 172:1-11). However, c-Kitis frequently expressed in colorectal carcinoma (Bellone, et al., 1997,J. Cell Physiol. 172: 1-11), and autocrine loops of SCF and c-Kit havebeen observed in several colon carcinoma cell lines (Toyota, et al.,1993, Turn Biol 14:295-302; Lahm, et al., 1995, Cell Growth & Differ6:1111-1118; Bellone, et al., 1997, J. Cell Physiol. 172:1-11).Furthermore, disruption of the autocrine loop by the use of neutralizingantibodies (Lahm, et al., 1995, Cell Growth & Differ. 6:1111-1118) anddownregulation of c-Kit and/or SCF significantly inhibits cellproliferation (Lahm, et al., 1995, Cell Growth & Differ 6:1111-1118;Bellone, et al., 1997, J. Cell Physiol. 172:1-11).

SCF/c-Kit autocrine loops have been observed in gastric carcinoma celllines (Turner, et al., 1992, Blood 80:374-381; Hassan, et al., 1998,Digest. Dis. Science 43:8-14), and constitutive c-Kit activation alsoappears to be important for gastrointestinal stromal tumors (GISTs).GISTs are the most common mesenchymal tumor of the digestive system.More than 90% of GISTs express c-Kit, which is consistent with theputative origin of these tumor cells from interstitial cells of Cajal(ICCs) (Hirota, et al., 1998, Science 279:577-580). ICCs are thought toregulate contraction of the gastrointestinal tract, and patients lackingc-Kit in their ICCs exhibited a myopathic form of chronic idiopathicintestinal pseudo-obstruction (Isozaki, et al., 1997, Amer. J. of Gast9:332-334). The c-Kit expressed in GISTs from several different patientswas observed to have mutations in the intracellular juxtamembrane domainleading to constitutive activation of this RTK (Hirota, et al., 1998,Science 279:577-580). Hence, inhibition of c-Kit kinase will be anefficacious means for the treatment of these cancers.

Testicular cancers: Male germ cell tumors have been histologicallycategorized into seminomas, which retain germ cell characteristics, andnonseminomas which can display characteristics of embryonaldifferentiation. Both seminomas and nonseminomas are thought to initiatefrom a preinvasive stage designated carcinoma in situ (CIS) (Murty, etal., 1998, Sem. Oncol. 25:133-144). Both c-Kit and SCF have beenreported to be essential for normal gonadal development duringembryogenesis (Loveland, et al., 1997, J. Endocrinol 153:337-344). Lossof either the receptor or the ligand resulted in animals devoid of germcells. In postnatal testes, c-Kit has been found to be expressed inLeydig cells and spermatogonia, while SCF was expressed in Sertoli cells(Loveland, et al., 1997, J. Endocrinol 153:337-344). Testicular tumorsdevelop from Leydig cells with high frequency in transgenic miceexpressing human papilloma virus 16 (HPV16) E6 and E7 oncogenes (Kondoh,et al., 1991, J. Virol. 65:3335-3339; Kondoh, et al., 1994, J. Urol.152:2151-2154). These tumors express both c-Kit and SCF, and anautocrine loop may contribute to the tumorigenesis (Kondoh, et al.,1995, Oncogene 10:341-347) associated with cellular loss of functionalp53 and the retinoblastoma gene product by association with E6 and E7(Dyson, et al., 1989, Science 243:934-937; Werness, et al., 1990,Science 248:76-79; Scheffner, et al., 1990, Cell 63:1129-1136).Defective signaling mutants of SCF (Kondoh, et al., 1995, Oncogene10:341-347) or c-Kit (Li, et al., 1996, Canc. Res. 56:4343-4346)inhibited formation of testicular tumors in mice expressing HPV16 E6 andE7. The c-Kit kinase activation is pivotal to tumorigenesis in theseanimals and thus modulation of the c-Kit kinase pathway by the presentinvention will prevent or treat such disorders.

Expression of c-Kit in germ cell tumors shows that the receptor isexpressed by the majority of carcinomas in situ and seminomas, but c-Kitis expressed in only a minority of nonseminomas (Strohmeyer, et al.,1991, Canc. Res. 51:1811-1816; Rajpert-de Meyts, et al., 1994, Int. J.Androl. 17:85-92; Izquierdo, et al., 1995, J. Pathol. 177:253-258;Strohmeyer, et al., 1995, J. Urol. 153:511-515; Bokenmeyer, et al.,1996, J. Cancer Res. Clin. Oncol. 122:301-306; Sandlow, et al., 1996, J.Androl. 17:403-408). Therefore, inhibition of c-Kit kinase provides ameans for treating these disorders.

CNS cancers: SCF and c-Kit are expressed throughout the CNS ofdeveloping rodents, and the pattern of expression indicates a role ingrowth, migration and differentiation of neuroectodermal cells.Expression of both receptor and ligand have also been reported in theadult brain (Hamel, et al., 1997, J. Neuro-One. 35:327-333). Expressionof c-Kit has also been observed in normal human brain tissue (Tada, etal. 1994, J. Neuro 80:1063-1073). Glioblastoma and astrocytoma, whichdefine the majority of intracranial tumors, arise from neoplastictransformation of astrocytes (Levin, et al., 1997, Principles & Practiceof Oncology:2022-2082). Expression of c-Kit has been observed inglioblastoma cell lines and tissues (Berdel, et al., 1992, Canc. Res.52:3498-3502; Tada, et al. 1994, J. Neuro 80:1063-1073; Stanulla, etal., 1995, Act Neuropath 89:158-165).

Cohen, et al., 1994, Blood 84:3465-3472 reported that all 14neuroblastoma cell lines examined contained c-Kit/SCF autocrine loops,and expression of both the receptor and ligand were observed in 45% oftumor samples examined. In two cell lines, anti-c-Kit antibodiesinhibited cell proliferation, suggesting that the SCF/c-Kit autocrineloop contributed to growth (Cohen, et al., 1994, Blood 84:3465-3472).Hence, c-Kit kinase inhibitors can be used to treat these cancers.

Exemplary Mast Cell Diseases Involving c-Kit

Excessive activation of c-Kit is also associated with diseases resultingfrom an over-abundance of mast cells. Mastocytosis is the term used todescribe a heterogeneous group of disorders characterized by excessivemast cell proliferation (Metcalfe, 1991, J. Invest. Derm 93:2 S-4S;Golkar, et al., 1997, Lancet 349:1379-1385). Elevated c-Kit expressionwas reported on mast cells from patients with aggressive mastocytosis(Nagata, et al. 1998, Leukemia 12:175-181).

Additionally, mast cells and eosinophils represent key cells involved inallergy, inflammation and asthma (Thomas, et al., 1996, Gen. Pharmacol27:593-597; Metcalfe, et al., 1997, Physiol Rev 77:1033-1079; Naclerio,et al., 1997, JAMA 278:1842-1848; Costa, et al., 1997, JAMA278:1815-1822). SCF, and hence c-Kit, directly and indirectly regulatesactivation of both mast cells and eosinophils, thereby influencing theprimary cells involved in allergy and asthma through multiplemechanisms. Because of this mutual regulation of mast cell andeosinophil function, and the role that SCF can play in this regulation,inhibition of c-Kit can be used to treat allergy-associated chronicrhinitis, inflammation and asthma.

Mastocytosis: SCF (also known as mast cell growth factor) stimulation ofc-Kit has been reported to be essential for the growth and developmentof mast cells (Hamel, et al., 1997, J. Neuro-One. 35:327-333; Kitamura,et al., 1995, Int. Arch. Aller. Immunol. 107:54-56). Mice with mutationsof c-Kit that attenuate its signaling activity have exhibitedsignificantly fewer mast cells in their skin (Tsujimura, 1996, PatholInt 46:933-938). Excessive activation of c-Kit can be associated withdiseases resulting from an over abundance of mast cells.

Mastocytosis is limited to the skin in the majority of patients, but caninvolve other organs in 15-20% of patients (Valent, 1996, Wein/KlinWochenschr 108:385-397; Golkar, et al., 1997, Lancet 349:1379-1385).Even among patients with systemic mastocytosis, the disease can rangefrom having a relatively benign prognosis to aggressive mastocytosis andmast cell leukemia. (Valent, 1996, Wein/Klin Wochenschr 108:385-397;Golkar, et al., 1997, Lancet 349:1379-1385). c-Kit has been observed onmalignant mast cells from canine mast cell tumors (London, et al., 1996,J. Compar. Pathol. 115:399-414), as well as on mast cells from patientswith aggressive systemic mastocytosis (Castells, et al., 1996, J. Aller.Clin. Immunol. 98:831-840).

SCF has been shown to be expressed on stromal cells as a membrane-boundprotein, and its expression can be induced by fibrogenic growth factorssuch as PDGF. It has also been shown to be expressed on keratinocytes asa membrane-bound protein in normal skin. However, in the skin ofpatients with mastocytosis, an increased amount of soluble SCF has beenobserved (Longley, et al., 1993, New Engl. J. Med. 328:1302-1307).

Mast cell chymase has been reported to cleave membrane-associated SCF toa soluble and biologically active form. This mast cell-mediated processcan generate a feedback loop to enhance mast cell proliferation andfunction (Longley, et al., 1997, Proc. Natl. Acad. Sci. 94:9017-9021),and may be important for the etiology of mastocytosis. Transgenic miceoverexpressing a form of SCF that could not be proteolytically releasedfrom keratinocytes did not develop mastocytosis, while similar animalsexpressing normal SCF in keratinocytes exhibited a phenotype resemblinghuman cutaneous mastocytosis (Kunisada, et al., 1998, J. Exp. Med.187:1565-1573). Formation of large amounts of soluble SCF can contributeto the pathology associated with mastocytosis in some patients and thepresent invention can treat or prevent such disorders by modulating theinteraction between SCF and c-Kit kinase. Several different mutations ofthe c-Kit RTK that resulted in constitutive kinase activity have beenfound in human and rodent mast cell tumor cell lines (Furitsu, et al.,1993, J. Clin. Invest. 92:1736-1744; Tsujimura, et al., 1994, Blood9:2619-2626; Tsujimura, et al., 1995, Int. Arch. Aller. Immunol106:377-385; Tsujimura, 1996, Pathol Int 46:933-938). In addition,activating mutations of the c-Kit gene have been observed in peripheralmononuclear cells isolated from patients with mastocytosis andassociated hematologic disorders (Nagata, et al., 1998, MastocytosisLeuk 12:175-181), and in mast cells from a patient with urticariapigmentosa and aggressive mastocytosis (Longley, et al., 1996, Nat. Gen.12:312-314). Inhibition of c-Kit kinase will therefore prove to have anexcellent therapeutic role in the treatment of these disorders.

In some patients, activating mutations of the c-Kit RTK may beresponsible for the pathogenesis of the disease and these patients canbe treated, or their diseases prevented, by modulation of the SCFinteraction with c-Kit kinase. SCF activation of c-Kit as been shown toprevent mast cell apoptosis which may be critical for maintainingcutaneous mast cell homeostasis (Iemura, et al., 1994, Amer. J Pathol144:321-328; Yee, et al., 1994, J. Exp. Med. 179:1777-1787; Mekori, etal., 1994, J. Immunol 153:2194-2203; Mekori, et al., 1995, Int. Arch.Allergy Immunol 107:137-138). Inhibition of mast cell apoptosis can leadto the mast cell accumulation associated with mastocytosis. Thus,observation of c-Kit activation resulting from overexpression of thereceptor, excessive formation of soluble SCF, or mutations of the c-Kitgene that constitutively activate its kinase, provides a rationale thatinhibition of the kinase activity of c-Kit will decrease the number ofmast cells and provide benefit for patients with mastocytosis.

For cells with activating c-Kit mutations, it was found that inhibitorsof c-Kit inhibit or even kill the cells (Ma et al., 2000, J InvestDermatol. 114:392-394), particularly for mutations in the regulatoryregion (Ma et al., 2002, Blood 99:1741-1744). Ma et al., 2002, alsoshowed that for mutations in the catalytic region, inhibitors ST1571(Gleevec) and SU9529 did not inhibit the cells, such that additionaltypes of c-Kit inhibitors are useful. Thus, c-Kit inhibitors can be usedagainst both wild-type c-Kit as well as c-Kit having mutations, e.g.,activating mutations in the regulatory region and/or catalytic region.

Asthma & Allergy: Mast cells and eosinophils represent key cells inparasitic infection, allergy, inflammation, and asthma (Thomas, et al.,1996, Gen. Pharmacol 27:593-597; Metcalfe, et al., 1997, Physiol Rev77:1033-1079; Holgate, 1997, CIBA Found. Symp.; Naclerio, et al, 1997,JAMA 278:1842-1848; Costa, et al., 1997, JAMA 778:1815-1822). SCF hasbeen shown to be essential for mast cell development, survival andgrowth (Kitamura, et al., 1995, Int. Arch. Aller. Immunol. 107:54-56;Metcalfe, et al., 1997, Physiol Rev 77:1033-1079). In addition, SCFcooperates with the eosinophil-specific regulator, IL-5, to increase thedevelopment of eosinophil progenitors (Metcalf, et al., 1998, Proc.Natl. Acad. Sci., USA 95:6408-6412). SCF has also been reported toinduce mast cells to secrete factors (Okayama, et al., 1997, Int. Arch.Aller. Immunol. 114:75-77; Okayama, et al., 1998, Eur. J. Immunol,28:708-715) that promote the survival of eosinophils (Kay, et al., 1997,Int. Arch. Aller. Immunol. 113:196-199), which may contribute tochronic, eosinophil-mediated inflammation (Okayama, et al., 1997, Int.Arch. Aller. Immunol. 114:75-77; Okayama, et al., 1998, Eur. J. Immunol.28:708-715). In this regard, SCF directly and indirectly regulatesactivation of both mast cells and eosinophils.

SCF induces mediator release from mast cells, as well as priming thesecells for IgE-induced degranulation (Columbo, et al., 1992, J. Imnunol149:599-602) and sensitizing their responsiveness to eosinophil-derivedgranule major basic protein (Furuta, et al., 1998, Blood 92:1055-1061).Among the factors released by activated mast cells are IL-5, GM-CSF andTNF-α, which influence eosinophil protein secretion (Okayama, et al.,1997, Int. Arch. Aller. Immunol. 114:75-77; Okayama, et al., 1998, Eur.J. Immunol. 28:708-715). In addition to inducing histamine release frommast cells (Luckacs, et al., 1996, J. Immunol. 156:3945-3951; Hogaboam,et al., 1998, J. Imnunol. 160:6166-6171), SCF promotes the mast cellproduction of the eosinophil chemotactic factor, eotaxin (Hogaboam, etal., 1998, J. Immunol. 160:6166-6171), and eosinophil infiltration(Luckacs, et al., 1996, J. Immunol. 156:3945-3951).

SCF also directly influences the adhesion of both mast cells (Dastych,et al., 1994, J. Immunol. 152:213-219; Kinashi, et al., 1994, Blood83:1033-1038) and eosinophils (Yuan, et al., 1997, J. Exp. Med.186:313-323), which in turn, regulates tissue infiltration. Thus, SCFcan influence the primary cells involved in allergy and asthma throughmultiple mechanisms. Currently, corticosteroids are the most effectivetreatment for chronic rhinitis and inflammation associated with allergy(Naclerio, et al., 1997, JAMA 278:1842-1848; Meltzer, 1997, Aller.52:33-40). These agents work through multiple mechanisms includingreduction of circulating and infiltrating mast cells and eosinophils,and diminished survival of eosinophils associated with inhibition ofcytokine production (Meltzer, 1997, Aller. 52:33-40). Steroids have alsobeen reported to inhibit the expression of SCF by fibroblasts andresident connective tissue cells, which leads to diminished mast cellsurvival (Finotto, et al., 1997, J. Clin. Invest. 99:1721-1728). Becauseof the mutual regulation of mast cell and eosinophil function, and therole that SCF can play in this regulation, inhibition of c-Kit kinaseprovides a means to treat allergy-associated chronic rhinitis,inflammation and asthma.

Inflammatory arthritis (e.g. rheumatoid arthritis): Due to theassociation of mast cells with the arthritic process (Lee et al., 2002,Science 297:1689-1692), c-Kit provides a useful target for prevention,delay, and/or treatment of inflammatory arthritis, such as rheumatoidarthritis.

Multiple sclerosis: Mast cells have been shown to play an extensive rolein autoimmune diseases, as demonstrated in experimental allergicencephalomyelitis (EAE), the mouse model of multiple sclerosis (MS).Mast cells were indicated to be required for full manifestation of thedisease. Secor et al., 2000, J Exp Med 191:813-821. Thus, c-Kit alsoprovides a useful target for the prevention, delay, and/or treatment ofmultiple sclerosis.

Modulators of c-Kit function thus can be used against diseases such asthose indicated above.

II. c-Kit Structures

A crystal structure of c-Kit with binding compound STI-571 (Gleevec) hasbeen reported, and atomic coordinates for that structure were depositedin the Protein Data Bank (PDB) as 1PKG, and in the Molecular ModelingDataBase as 23938. Such a structure can be used for modeling the bindingof different compounds by replacing STI-571 with another compound. Forexample, using convention molecular modeling software, coordinates forSTI-571 can be removed, and replaced with coordinates for anothercompound. The structure is allowed to adjust to reflect binding of thereplacement compound.

Similarly to the reported structure, co-crystals of c-Kit with acompound of Formula I can be formed and analyzed to provide co-crystalstructures.

It is to be understood that the crystalline kinases and kinase domainsof the invention are not limited to naturally occurring or nativekinase. Indeed, the crystals of the invention include crystals ofmutants of native kinases. Mutants of native kinases are obtained byreplacing at least one amino acid residue in a native kinase with adifferent amino acid residue, or by adding or deleting amino acidresidues within the native polypeptide or at the N- or C-terminus of thenative polypeptide, and have substantially the same three-dimensionalstructure as the native kinase from which the mutant is derived.

By having substantially the same three-dimensional structure is meanthaving a set of atomic structure coordinates that have aroot-mean-square deviation of less than or equal to about 2 Å whensuperimposed with the atomic structure coordinates of the native kinasefrom which the mutant is derived when at least about 50% to 100% of theCα atoms of the native kinase domain are included in the superposition.

Amino acid substitutions, deletions and additions which do notsignificantly interfere with the three-dimensional structure of thekinase will depend, in part, on the region of the kinase where thesubstitution, addition or deletion occurs. In highly variable regions ofthe molecule, non-conservative substitutions as well as conservativesubstitutions may be tolerated without significantly disrupting thethree-dimensional, structure of the molecule. In highly conservedregions, or regions containing significant secondary structure,conservative amino acid substitutions are preferred. Such conserved andvariable regions can be identified by sequence alignment of c-Kit withother kinases.

Conservative amino acid substitutions are well known in the art, andinclude substitutions made on the basis of similarity in polarity,charge, solubility, hydrophobicity, hydrophilicity and/or theamphipathic nature of the amino acid residues involved. For example,negatively charged amino acids include aspartic acid and glutamic acid;positively charged amino acids include lysine and arginine; amino acidswith uncharged polar head groups having similar hydrophilicity valuesinclude the following: leucine, isoleucine, valine; glycine, alanine;asparagine, glutamine; serine, threonine; phenylalanine, tyrosine. Otherconservative amino acid substitutions are well known in the art.

For c-Kit obtained in whole or in part by chemical synthesis, theselection of amino acids available for substitution or addition is notlimited to the genetically encoded amino acids. Indeed, the mutantsdescribed herein may contain non-genetically encoded amino acids.Conservative amino acid substitutions for many of the commonly knownnon-genetically encoded amino acids are well known in the art.Conservative substitutions for other amino acids can be determined basedon their physical properties as compared to the properties of thegenetically encoded amino acids.

In some instances, it may be particularly advantageous or convenient tosubstitute, delete and/or add amino acid residues to a native kinase inorder to provide convenient cloning sites in cDNA encoding thepolypeptide, to aid in purification of the polypeptide, and forcrystallization of the polypeptide. Such substitutions, deletions and/oradditions which do not substantially alter the three dimensionalstructure of the native kinase domain will be apparent to those ofordinary skill in the art.

It should be noted that the mutants contemplated herein need not allexhibit kinase activity. Indeed, amino acid substitutions, additions ordeletions that interfere with the kinase activity but which do notsignificantly alter the three-dimensional structure of the domain arespecifically contemplated by the invention. Such crystallinepolypeptides, or the atomic structure coordinates obtained therefrom,can be used to identify compounds that bind to the native domain. Thesecompounds can affect the activity of the native domain.

The derivative crystals of the invention can comprise a crystallinekinase polypeptide in covalent association with one or more heavy metalatoms. The polypeptide may correspond to a native or a mutated kinase.Heavy metal atoms useful for providing derivative crystals include, byway of example and not limitation, gold, mercury, selenium, etc.

The co-crystals of the invention generally comprise a crystalline kinasedomain polypeptide in association with one or more compounds. Theassociation may be covalent or non-covalent. Such compounds include, butare not limited to, cofactors, substrates, substrate analogues,inhibitors, allosteric effectors, etc.

III. Three Dimensional Structure Determination Using X-rayCrystallography

X-ray crystallography is a method of solving the three dimensionalstructures of molecules. The structure of a molecule is calculated fromX-ray diffraction patterns using a crystal as a diffraction grating.Three dimensional structures of protein molecules arise from crystalsgrown from a concentrated aqueous solution of that protein. The processof X-ray crystallography can include the following steps:

-   -   (a) synthesizing and isolating (or otherwise obtaining) a        polypeptide;    -   (b) growing a crystal from an aqueous solution comprising the        polypeptide with or without a modulator; and    -   (c) collecting X-ray diffraction patterns from the crystals,        determining unit cell dimensions and symmetry, determining        electron density, fitting the amino acid sequence of the        polypeptide to the electron density, and refining the structure.

Production of Polypeptides

The native and mutated kinase polypeptides described herein may bechemically synthesized in whole or part using techniques that arewell-known in the art (see, e.g., Creighton (1983) Biopolymers22(1):49-58).

Alternatively, methods which are well known to those skilled in the artcan be used to construct expression vectors containing the native ormutated kinase polypeptide coding sequence and appropriatetranscriptional/translational control signals. These methods include invitro recombinant DNA techniques, synthetic techniques and in vivorecombination/genetic recombination. See, for example, the techniquesdescribed in Maniatis, T (1989). Molecular cloning: A laboratory Manual.Cold Spring Harbor Laboratory, New York. Cold Spring Harbor LaboratoryPress; and Ausubel, F. M. et al. (1994) Current Protocols in MolecularBiology. John Wiley & Sons, Secaucus, N.J.

A variety of host-expression vector systems may be utilized to expressthe kinase coding sequence. These include but are not limited tomicroorganisms such as bacteria transformed with recombinantbacteriophage DNA, plasmid DNA or cosmid DNA expression vectorscontaining the kinase domain coding sequence; yeast transformed withrecombinant yeast expression vectors containing the kinase domain codingsequence; insect cell systems infected with recombinant virus expressionvectors (e.g., baculovirus) containing the kinase domain codingsequence; plant cell systems infected with recombinant virus expressionvectors (e.g., cauliflower mosaic virus, CaMV; tobacco mosaic virus,TMV) or transformed with recombinant plasmid expression vectors (e.g.,Ti plasmid) containing the kinase domain coding sequence; or animal cellsystems. The expression elements of these systems vary in their strengthand specificities.

Depending on the host/vector system utilized, any of a number ofsuitable transcription and translation elements, including constitutiveand inducible promoters, may be used in the expression vector. Forexample, when cloning in bacterial systems, inducible promoters such aspL of bacteriophage λ, plac, ptrp, ptac (ptrp-lac hybrid promoter) andthe like may be used; when cloning in insect cell systems, promoterssuch as the baculovirus polyhedrin promoter may be used; when cloning inplant cell systems, promoters derived from the genome of plant cells(e.g., heat shock promoters; the promoter for the small subunit ofRUBISCO; the promoter for the chlorophyll a/b binding protein) or fromplant viruses (e.g., the 35S RNA promoter of CaMV; the coat proteinpromoter of TMV) may be used; when cloning in mammalian cell systems,promoters derived from the genome of mammalian cells (e.g.,metallothionein promoter) or from mammalian viruses (e.g., theadenovirus late promoter; the vaccinia virus 7.5K promoter) may be used;when generating cell lines that contain multiple copies of the kinasedomain DNA, SV4O-, BPV- and EBV-based vectors may be used with anappropriate selectable marker.

Exemplary methods describing methods of DNA manipulation, vectors,various types of cells used, methods of incorporating the vectors intothe cells, expression techniques, protein purification and isolationmethods, and protein concentration methods are disclosed in detail inPCT publication WO 96/18738. This publication is incorporated herein byreference in its entirety, including any drawings. Those skilled in theart will appreciate that such descriptions are applicable to the presentinvention and can be easily adapted to it.

Crystal Growth

Crystals are grown from an aqueous solution containing the purified andconcentrated polypeptide by a variety of techniques. These techniquesinclude batch, liquid, bridge, dialysis, vapor diffusion, and hangingdrop methods. McPherson (1982) John Wiley, New York; McPherson (1990)Eur. J. Biochem. 189:1-23; Webber (1991) Adv. Protein Chem. 41:1-36,incorporated by reference herein in their entireties, including allfigures, tables, and drawings.

The native crystals of the invention are, in general, grown by addingprecipitants to the concentrated solution of the polypeptide. Theprecipitants are added at a concentration just below that necessary toprecipitate the protein. Water is removed by controlled evaporation toproduce precipitating conditions, which are maintained until crystalgrowth ceases.

For crystals of the invention, exemplary crystallization conditions aredescribed in the Examples. Those of ordinary skill in the art willrecognize that the exemplary crystallization conditions can be varied.Such variations may be used alone or in combination. In addition, othercrystallization conditions may be found, e.g., by using crystallizationscreening plates to identify such other conditions. Those alternateconditions can then be optimized if needed to provide larger or betterquality crystals.

Derivative crystals of the invention can be obtained by soaking nativecrystals in mother liquor containing salts of heavy metal atoms. It hasbeen found that soaking a native crystal in a solution containing about0.1 mM to about 5 mM thimerosal, 4-chloromeruribenzoic acid or KAu(CN)₂for about 2 hr to about 72 hr provides derivative crystals suitable foruse as isomorphous replacements in determining the X-ray crystalstructure.

Co-crystals of the invention can be obtained by soaking a native crystalin mother liquor containing compound that binds the kinase, or can beobtained by co-crystallizing the kinase polypeptide in the presence of abinding compound.

Generally, co-crystallization of kinase and binding compound can beaccomplished using conditions identified for crystallizing thecorresponding kinase without binding compound. It is advantageous if aplurality of different crystallization conditions have been identifiedfor the kinase, and these can be tested to determine which conditiongives the best co-crystals. It may also be beneficial to optimize theconditions for co-crystallization. Alternatively, new crystallizationconditions can be determined for obtaining co-crystals, e.g., byscreening for crystallization and then optimizing those conditions.Exemplary co-crystallization conditions are provided in the Examples.

Determining Unit Cell Dimensions and the Three Dimensional Structure ofa Polypeptide or Polypeptide Complex

Once the crystal is grown, it can be placed in a glass capillary tube orother mounting device and mounted onto a holding device connected to anX-ray generator and an X-ray detection device. Collection of X-raydiffraction patterns are well documented by those in the art. See, e.g.,Ducruix and Geige, (1992), IRL Press, Oxford, England, and referencescited therein. A beam of X-rays enters the crystal and then diffractsfrom the crystal. An X-ray detection device can be utilized to recordthe diffraction patterns emanating from the crystal. Although the X-raydetection device on older models of these instruments is a piece offilm, modern instruments digitally record X-ray diffraction scattering.X-ray sources can be of various types, but advantageously, a highintensity source is used, e.g., a synchrotron beam source.

Methods for obtaining the three dimensional structure of the crystallineform of a peptide molecule or molecule complex are well known in theart. See, e.g., Ducruix and Geige, (1992), IRL Press, Oxford, England,and references cited therein. The following are steps in the process ofdetermining the three dimensional structure of a molecule or complexfrom X-ray diffraction data.

After the X-ray diffraction patterns are collected from the crystal, theunit cell dimensions and orientation in the crystal can be determined.They can be determined from the spacing between the diffractionemissions as well as the patterns made from these emissions. The unitcell dimensions are characterized in three dimensions in units ofAngstroms (one Å=10⁻¹⁰ meters) and by angles at each vertices. Thesymmetry of the unit cell in the crystals is also characterized at thisstage. The symmetry of the unit cell in the crystal simplifies thecomplexity of the collected data by identifying repeating patterns.Application of the symmetry and dimensions of the unit cell is describedbelow.

Each diffraction pattern emission is characterized as a vector and thedata collected at this stage of the method determines the amplitude ofeach vector. The phases of the vectors can be determined using multipletechniques. In one method, heavy atoms can be soaked into a crystal, amethod called isomorphous replacement, and the phases of the vectors canbe determined by using these heavy atoms as reference points in theX-ray analysis. (Otwinowski, (1991), Daresbury, United Kingdom, 80-86).The isomorphous replacement method usually utilizes more than one heavyatom derivative.

In another method, the amplitudes and phases of vectors from acrystalline polypeptide with an already determined structure can beapplied to the amplitudes of the vectors from a crystalline polypeptideof unknown structure and consequently determine the phases of thesevectors. This second method is known as molecular replacement and theprotein structure which is used as a reference must have a closelyrelated structure to the protein of interest. (Naraza (1994) Proteins1:281-296). Thus, the vector information from a kinase of knownstructure, such as those reported herein, are useful for the molecularreplacement analysis of another kinase with unknown structure.

Once the phases of the vectors describing the unit cell of a crystal aredetermined, the vector amplitudes and phases, unit cell dimensions, andunit cell symmetry can be used as terms in a Fourier transform function.The Fourier transform function calculates the electron density in theunit cell from these measurements. The electron density that describesone of the molecules or one of the molecule complexes in the unit cellcan be referred to as an electron density map. The amino acid structuresof the sequence or the molecular structures of compounds complexed withthe crystalline polypeptide may then be fitted to the electron densityusing a variety of computer programs. This step of the process issometimes referred to as model building and can be accomplished by usingcomputer programs such as Turbo/FRODO or “O”. (Jones (1985) Methods inEnzymology 115:157-171).

A theoretical electron density map can then be calculated from the aminoacid structures fit to the experimentally determined electron density.The theoretical and experimental electron density maps can be comparedto one another and the agreement between these two maps can be describedby a parameter called an R-factor. A low value for an R-factor describesa high degree of overlapping electron density between a theoretical andexperimental electron density map.

The R-factor is then minimized by using computer programs that refinethe theoretical electron density map. A computer program such as X-PLORcan be used for model refinement by those skilled in the art. (Brünger(1992) Nature 355:472-475.) Refinement may be achieved in an iterativeprocess. A first step can entail altering the conformation of atomsdefined in an electron density map. The conformations of the atoms canbe altered by simulating a rise in temperature, which will increase thevibrational frequency of the bonds and modify positions of atoms in thestructure. At a particular point in the atomic perturbation process, aforce field, which typically defines interactions between atoms in termsof allowed bond angles and bond lengths, Van der Waals interactions,hydrogen bonds, ionic interactions, and hydrophobic interactions, can beapplied to the system of atoms. Favorable interactions may be describedin terms of free energy and the atoms can be moved over many iterationsuntil a free energy minimum is achieved. The refinement process can beiterated until the R-factor reaches a minimum value.

The three dimensional structure of the molecule or molecule complex isdescribed by atoms that fit the theoretical electron densitycharacterized by a minimum R-value. A file can then be created for thethree dimensional structure that defines each atom by coordinates inthree dimensions.

IV. Structures of c-Kit Binding Site

High-resolution three-dimensional structures and atomic structurecoordinates of crystalline c-Kit kinase domain with binding compoundhave been determined.

Those having skill in the art will recognize that atomic structurecoordinates as determined by X-ray crystallography are not withouterror. Thus, it is to be understood that generally any set of structurecoordinates obtained for crystals of a kinase, whether native crystals,kinase domain crystals, derivative crystals or co-crystals, that have aroot mean square deviation (“r.m.s.d.”) of less than or equal to about1.5 Å when superimposed, using backbone atoms (N, C_(α), C and 0), onthe structure coordinates listed in a coordinate table herein areconsidered to be identical with the structure coordinates listed in thattable when at least about 50% to 100% of the backbone atoms of thecrystallized protein are included in the superposition.

V. Uses of the Crystals and Atomic Structure Coordinates

The crystals of the invention, and particularly the atomic structurecoordinates obtained therefrom, have a wide variety of uses. Forexample, the crystals described herein can be used as a starting pointin any of the methods of use for kinases known in the art or laterdeveloped. Such methods of use include, for example, identifyingmolecules that bind to the native or mutated catalytic domain ofkinases. The crystals and structure coordinates are particularly usefulfor identifying ligands that modulate kinase activity as an approachtowards developing new therapeutic agents. In particular, the crystalsand structural information are useful in methods for ligand developmentutilizing molecular scaffolds.

The structure coordinates described herein can be used as phasing modelsfor determining the crystal structures of additional kinases, as well asthe structures of co-crystals of such kinases with ligands such asinhibitors, agonists, antagonists, and other molecules. The structurecoordinates, as well as models of the three-dimensional structuresobtained therefrom, can also be used to aid the elucidation ofsolution-based structures of native or mutated kinases, such as thoseobtained via NMR.

VI. Electronic Representations of c-Kit Structures

Structural information of kinases or portions of kinases (e.g., kinaseactive sites) can be represented in many different ways. Particularlyuseful are electronic representations, as such representations allowrapid and convenient data manipulations and structural modifications.Electronic representations can be embedded in many different storage ormemory media, frequently computer readable media. Examples includewithout limitations, computer random access memory (RAM), floppy disk,magnetic hard drive, magnetic tape (analog or digital), compact disk(CD), optical disk, CD-ROM, memory card, digital video disk (DVD), andothers. The storage medium can be separate or part of a computer system.Such a computer system may be a dedicated, special purpose, or embeddedsystem, such as a computer system that forms part of an X-raycrystallography system, or may be a general purpose computer (which mayhave data connection with other equipment such as a sensor device in anX-ray crystallographic system. In many cases, the information providedby such electronic representations can also be represented physically orvisually in two or three dimensions, e.g., on paper, as a visual display(e.g., on a computer monitor as a two dimensional or pseudo-threedimensional image) or as a three dimensional physical model. Suchphysical representations can also be used, alone or in connection withelectronic representations. Exemplary useful representations include,but are not limited to, the following:

Atomic Coordinate Representation

One type of representation is a list or table of atomic coordinatesrepresenting positions of particular atoms in a molecular structure,portions of a structure, or complex (e.g., a co-crystal). Such arepresentation may also include additional information, for example,information about occupancy of particular coordinates.

Energy Surface or Surface of Interaction Representation

Another representation is an energy surface representation, e.g., of anactive site or other binding site, representing an energy surface forelectronic and steric interactions. Such a representation may alsoinclude other features. An example is the inclusion of representation ofa particular amino acid residue(s) or group(s) on a particular aminoacid residue(s), e.g., a residue or group that can participate inH-bonding or ionic interaction. Such energy surface representations canbe readily generated from atomic coordinate representations using any ofa variety of available computer programs.

Structural Representation

Still another representation is a structural representation, i.e., aphysical representation or an electronic representation of such aphysical representation. Such a structural representation includesrepresentations of relative positions of particular features of amolecule or complex, often with linkage between structural features. Forexample, a structure can be represented in which all atoms are linked;atoms other than hydrogen are linked; backbone atoms, with or withoutrepresentation of sidechain atoms that could participate in significantelectronic interaction, are linked; among others. However, not allfeatures need to be linked. For example, for structural representationsof portions of a molecule or complex, structural features significantfor that feature may be represented (e.g., atoms of amino acid residuesthat can have significant binding interation with a ligand at a bindingsite. Those amino acid residues may not be linked with each other.

A structural representation can also be a schematic representation. Forexample, a schematic representation can represent secondary and/ortertiary structure in a schematic manner. Within such a schematicrepresentation of a polypeptide, a particular amino acid residue(s) orgroup(s) on a residue(s) can be included, e.g., conserved residues in abinding site, and/or residue(s) or group(s) that may interact withbinding compounds. Electronic structural representations can begenerated, for example, from atomic coordinate information usingcomputer programs designed for that function and/or by constructing anelectronic representation with manual input based on interpretation ofanother form of structural information. Physical representations can becreated, for example, by printing an image of a computer-generated imageor by constructing a 3D model. An example of such a printedrepresentation is the ribbon diagram presented in FIG. 2.

VII. Structure Determination for Kinases with Unknown Structure UsingStructural Coordinates

Structural coordinates, such as those available for c-Kit, can be usedto determine the three dimensional structures of kinases with unknownstructure. The methods described below can apply structural coordinatesof a polypeptide with known structure to another data set, such as anamino acid sequence, X-ray crystallographic diffraction data, or nuclearmagnetic resonance (NMR) data. Preferred embodiments of the inventionrelate to determining the three dimensional structures of modifiedkinases, other native kinases, and related polypeptides.

Structures Using Amino Acid Homology

Homology modeling is a method of applying structural coordinates of apolypeptide of known structure to the amino acid sequence of apolypeptide of unknown structure. This method is accomplished using acomputer representation of the three dimensional structure of apolypeptide or polypeptide complex, the computer representation of aminoacid sequences of the polypeptides with known and unknown structures,and standard computer representations of the structures of amino acids.Homology modeling generally involves (a) aligning the amino acidsequences of the polypeptides with and without known structure; (b)transferring the coordinates of the conserved amino acids in the knownstructure to the corresponding amino acids of the polypeptide of unknownstructure; refining the subsequent three dimensional structure; and (d)constructing structures of the rest of the polypeptide. One skilled inthe art recognizes that conserved amino acids between two proteins canbe determined from the sequence alignment step in step (a).

The above method is well known to those skilled in the art, (Greer(1985) Science 228:1055; Blundell et al A (1988) Eur. J. Biochem.172:513. An exemplary computer program that can be utilized for homologymodeling by those skilled in the art is the Homology module in theInsight II modeling package distributed by Accelerys Inc.

Alignment of the amino acid sequence is accomplished by first placingthe computer representation of the amino acid sequence of a polypeptidewith known structure above the amino acid sequence of the polypeptide ofunknown structure. Amino acids in the sequences are then compared andgroups of amino acids that are homologous (e.g., amino acid side chainsthat are similar in chemical nature—aliphatic, aromatic, polar, orcharged) are grouped together. This method will detect conserved regionsof the polypeptides and account for amino acid insertions or deletions.Such alignment and/or can also be performed fully electronically usingsequence alignment and analyses software.

Once the amino acid sequences of the polypeptides with known and unknownstructures are aligned, the structures of the conserved amino acids inthe computer representation of the polypeptide with known structure aretransferred to the corresponding amino acids of the polypeptide whosestructure is unknown. For example, a tyrosine in the amino acid sequenceof known structure may be replaced by a phenylalanine, the correspondinghomologous amino acid in the amino acid sequence of unknown structure.

The structures of amino acids located in non-conserved regions are to beassigned manually by either using standard peptide geometries ormolecular simulation techniques, such as molecular dynamics. The finalstep in the process is accomplished by refining the entire structureusing molecular dynamics and/or energy minimization. The homologymodeling method is well known to those skilled in the art and has beenpracticed using different protein molecules. For example, the threedimensional structure of the polypeptide corresponding to the catalyticdomain of a serine/threonine protein kinase, myosin light chain proteinkinase, was homology modeled from the cAMP-dependent protein kinasecatalytic subunit. (Knighton et al. (1992) Science 258:130-135.)

Structures Using Molecular Replacement

Molecular replacement is a method of applying the X-ray diffraction dataof a polypeptide of known structure to the X-ray diffraction data of apolypeptide of unknown sequence. This method can be utilized to definethe phases describing the X-ray diffraction data of a polypeptide ofunknown structure when only the amplitudes are known. X-PLOR is acommonly utilized computer software package used for molecularreplacement. Brünger (1992) Nature 355:472-475. AMORE is another programused for molecular replacement. Navaza (1994) Acta Crystallogr. A50:157-163. Preferably, the resulting structure does not exhibit aroot-mean-square deviation of more than 3 Å.

A goal of molecular replacement is to align the positions of atoms inthe unit cell by matching electron diffraction data from two crystals. Aprogram such as X-PLOR can involve four steps. A first step can be todetermine the number of molecules in the unit cell and define the anglesbetween them. A second step can involve rotating the diffraction data todefine the orientation of the molecules in the unit cell. A third stepcan be to translate the electron density in three dimensions tocorrectly position the molecules in the unit cell. Once the amplitudesand phases of the X-ray diffraction data is determined, an R-factor canbe calculated by comparing electron diffraction maps calculatedexperimentally from the reference data set and calculated from the newdata set. An R-factor between 30-50% indicates that the orientations ofthe atoms in the unit cell are reasonably determined by this method. Afourth step in the process can be to decrease the R-factor to roughly20% by refining the new electron density map using iterative refinementtechniques described herein and known to those or ordinary skill in theart.

Structures Using NMR Data

Structural coordinates of a polypeptide or polypeptide complex derivedfrom X-ray crystallographic techniques can be applied towards theelucidation of three dimensional structures of polypeptides from nuclearmagnetic resonance (NMR) data. This method is used by those skilled inthe art. (Wuthrich, (1986), John Wiley and Sons, New York: 176-199;Pflugrath et al. (1986) J. Mol. Biol. 189:383-386; Kline et al. (1986)J. Mol. Biol. 189:377-382.) While the secondary structure of apolypeptide is often readily determined by utilizing two-dimensional NMRdata, the spatial connections between individual pieces of secondarystructure are not as readily determinable. The coordinates defining athree-dimensional structure of a polypeptide derived from X-raycrystallographic techniques can guide the NMR spectroscopist to anunderstanding of these spatial interactions between secondary structuralelements in a polypeptide of related structure.

The knowledge of spatial interactions between secondary structuralelements can greatly simplify Nuclear Overhauser Effect (NOE) data fromtwo-dimensional NMR experiments. Additionally, applying thecrystallographic coordinates after the determination of secondarystructure by NMR techniques only simplifies the assignment of NOEsrelating to particular amino acids in the polypeptide sequence and doesnot greatly bias the NMR analysis of polypeptide structure. Conversely,using the crystallographic coordinates to simplify NOE data whiledetermining secondary structure of the polypeptide would bias the NMRanalysis of protein structure.

VIII. Structure-Based Design of Modulators of c-Kit Function UtilizingStructural Coordinates

Structure-based modulator design and identification methods are powerfultechniques that can involve searches of computer databases containing awide variety of potential modulators and chemical functional groups. Thecomputerized design and identification of modulators is useful as thecomputer databases contain more compounds than the chemical libraries,often by an order of magnitude. For reviews of structure-based drugdesign and identification (see Wuthrich, (1986), John Wiley and Sons,New York: 176-199; Pflugrath et al. (1986) J. Mol. Biol. 189:383-386,Kline et al. (1986) J. Mol. Biol. 189:377-382.).

The three dimensional structure of a polypeptide defined by structuralcoordinates can be utilized by these design methods. In addition, thethree dimensional structures of kinases determined by the homology,molecular replacement, and NMR techniques described herein can also beapplied to modulator design and identification methods.

For identifying modulators, structural information for a native kinase,in particular, structural information for the active site of the kinase,can be used. However, it may be advantageous to utilize structuralinformation from one or more co-crystals of the kinase with one or morebinding compounds. It can also be advantageous if the binding compoundhas a structural core in common with test compounds.

Design by Searching Molecular Data Bases

One method of rational design searches for modulators by docking thecomputer representations of compounds from a database of molecules.Publicly available databases include, for example:

-   -   a) ACD from Molecular Designs Limited    -   b) NCI from National Cancer Institute    -   c) CCDC from Cambridge Crystallographic Data Center    -   d) CAST from Chemical Abstract Service    -   e) Derwent from Derwent Information Limited    -   f) Maybridge from Maybridge Chemical Company LTD    -   g) Aldrich from Aldrich Chemical Company    -   h) Directory of Natural Products from Chapman & Hall

One such data base (ACD distributed by Molecular Designs LimitedInformation Systems) contains compounds that are synthetically derivedor are natural products. Methods available to those skilled in the artcan convert a data set represented in two dimensions to one representedin three dimensions. These methods are enabled by such computer programsas CONCORD from Tripos Associates or DE-Converter from MolecularSimulations Limited.

Multiple methods of structure-based modulator design are known to thosein the art. (Kuntz et al., (1982), J. Mol. Biol. 162: 269; Kuntz et al.,(1994), Acc. Chem. Res. 27: 117; Meng et al., (1992), J. Compt. Chem.13: 505; Bohm, (1994), J. Comp. Aided Molec. Design 8: 623.)

A computer program widely utilized by those skilled in the art ofrational modulator design is DOCK from the University of California inSan Francisco. The general methods utilized by this computer program andprograms like it are described in three applications below. Moredetailed information regarding some of these techniques can be found inthe Accelerys User Guide, 1995. A typical computer program used for thispurpose can perform a processes comprising the following steps orfunctions:

-   -   (a) remove the existing compound from the protein;    -   (b) dock the structure of another compound into the active-site        using the computer program (such as DOCK) or by interactively        moving the compound into the active-site;    -   (c) characterize the space between the compound and the        active-site atoms;    -   (d) search libraries for molecular fragments which (i) can fit        into the empty space between the compound and the active-site,        and (ii) can be linked to the compound; and    -   (e) link the fragments found above to the compound and evaluate        the new modified compound.

Part (c) refers to characterizing the geometry and the complementaryinteractions formed between the atoms of the active site and thecompounds. A favorable geometric fit is attained when a significantsurface area is shared between the compound and active-site atomswithout forming unfavorable steric interactions. One skilled in the artwould note that the method can be performed by skipping parts (d) and(e) and screening a database of many compounds.

Structure-based design and identification of modulators of kinasefunction can be used in conjunction with assay screening. As largecomputer databases of compounds (around 10,000 compounds) can besearched in a matter of hours or even less, the computer-based methodcan narrow the compounds tested as potential modulators of kinasefunction in biochemical or cellular assays.

The above descriptions of structure-based modulator design are not allencompassing and other methods are reported in the literature and can beused, e.g.:

-   -   (1) CAVEAT: Bartlett et al., (1989), in Chemical and Biological        Problems in Molecular Recognition, Roberts, S. M.; Ley, S. V.;        Campbell, M. M. eds.; Royal Society of Chemistry: Cambridge, pp.        182-196.    -   (2) FLOG: Miller et al., (1994), J. Comp. Aided Molec. Design        8:153.    -   (3) PRO Modulator: Clark et al, (1995), J. Comp. Aided Molec.        Design 9:13.    -   (4) MCSS: Miranker and Karplus, (1991), Proteins: Structure,        Function, and Genetics 11:29.    -   (5) AUTODOCK: Goodsell and Olson, (1990), Proteins. Structure,        Function, and Genetics 8: 195.    -   (6) GRID: Goodford, (1985) J. Med. Chem. 28:849.

Design by Modifying Compounds in Complex with c-Kit

Another way of identifying compounds as potential modulators is tomodify an existing modulator in the polypeptide active site. Forexample, the computer representation of modulators can be modifiedwithin the computer representation of a c-Kit active site. Detailedinstructions for this technique can be found, for example, in theAccelerys User Manual, 1995 in LUDI. The computer representation of themodulator is typically modified by the deletion of a chemical group orgroups or by the addition of a chemical group or groups.

Upon each modification to the compound, the atoms of the modifiedcompound and active site can be shifted in conformation and the distancebetween the modulator and the active-site atoms may be scored along withany complementary interactions formed between the two molecules. Scoringcan be complete when a favorable geometric fit and favorablecomplementary interactions are attained. Compounds that have favorablescores are potential modulators.

Design by Modifying the Structure of Compounds that Bind c-Kit

A third method of structure-based modulator design is to screencompounds designed by a modulator building or modulator searchingcomputer program. Examples of these types of programs can be found inthe Molecular Simulations Package, Catalyst, Descriptions for using thisprogram are documented in the Molecular Simulations User Guide (1995).Other computer programs used in this application are ISIS/HOST,ISIS/BASE, ISIS/DRAW) from Molecular Designs Limited and UNITY fromTripos Associates.

These programs can be operated on the structure of a compound that hasbeen removed from the active site of the three dimensional structure ofa compound-kinase complex. Operating the program on such a compound ispreferable since it is in a biologically active conformation.

A modulator construction computer program is a computer program that maybe used to replace computer representations of chemical groups in acompound complexed with a kinase or other biomolecule with groups from acomputer database. A modulator searching computer program is a computerprogram that may be used to search computer representations of compoundsfrom a computer data base that have similar three dimensional structuresand similar chemical groups as compound bound to a particularbiomolecule.

A typical program can operate by using the following general steps:

-   -   (a) map the compounds by chemical features such as by hydrogen        bond donors or acceptors, hydrophobic/lipophilic sites,        positively ionizable sites, or negatively ionizable sites;    -   (b) add geometric constraints to the mapped features; and    -   (c) search databases with the model generated in (b).

Those skilled in the art also recognize that not all of the possiblechemical features of the compound need be present in the model of (b).One can use any subset of the model to generate different models fordata base searches.

Modulator Design Using Molecular Scaffolds

The present invention can also advantageously utilize methods fordesigning compounds, designated as molecular scaffolds, that can actbroadly across families of molecules and/or for using a molecularscaffold to design ligands that target individual or multiple members ofthose families. Such design using molecular scaffolds is described inHirth and Milburn, U.S. patent application Ser. No. 10/377,268, which isincorporated herein by reference in its entirety. Such design anddevelopment using molecular scaffolds is described, in part, below.

In preferred embodiments, the molecules can be proteins and a set ofchemical compounds can be assembled that have properties such that theyare 1) chemically designed to act on certain protein families and/or 2)behave more like molecular scaffolds, meaning that they have chemicalsubstructures that make them specific for binding to one or moreproteins in a family of interest. Alternatively, molecular scaffolds canbe designed that are preferentially active on an individual targetmolecule.

Useful chemical properties of molecular scaffolds can include one ormore of the following characteristics, but are not limited thereto: anaverage molecular weight below about 350 daltons, or between from about150 to about 350 daltons, or from about 150 to about 300 daltons; havinga clogP below 3; a number of rotatable bonds of less than 4; a number ofhydrogen bond donors and acceptors below 5 or below 4; a polar surfacearea of less than 50 Å²; binding at protein binding sites in anorientation so that chemical substituents from a combinatorial librarythat are attached to the scaffold can be projected into pockets in theprotein binding site; and possessing chemically tractable structures atits substituent attachment points that can be modified, thereby enablingrapid library construction.

By “clog P” is meant the calculated log P of a compound, “P” referringto the partition coefficient between octanol and water.

The term “Molecular Polar Surface Area (PSA)” refers to the sum ofsurface contributions of polar atoms (usually oxygens, nitrogens andattached hydrogens) in a molecule. The polar surface area has been shownto correlate well with drug transport properties, such as intestinalabsorption, or blood-brain barrier penetration.

Additional useful chemical properties of distinct compounds forinclusion in a combinatorial library include the ability to attachchemical moieties to the compound that will not interfere with bindingof the compound to at least one protein of interest, and that willimpart desirable properties to the library members, for example, causingthe library members to be actively transported to cells and/or organs ofinterest, or the ability to attach to a device such as a chromatographycolumn (e.g., a streptavidin column through a molecule such as biotin)for uses such as tissue and proteomics profiling purposes.

A person of ordinary skill in the art will realize other properties thatcan be desirable for the scaffold or library members to have dependingon the particular requirements of the use, and that compounds with theseproperties can also be sought and identified in like manner. Methods ofselecting compounds for assay are known to those of ordinary skill inthe art, for example, methods and compounds described in U.S. Pat. Nos.6,288,234, 6,090,912, 5,840,485, each of which is hereby incorporated byreference in its entirety, including all charts and drawings.

In various embodiments, the present invention provides methods ofdesigning ligands that bind to a plurality of members of a molecularfamily, where the ligands contain a common molecular scaffold. Thus, acompound set can be assayed for binding to a plurality of members of amolecular family, e.g., a protein family. One or more compounds thatbind to a plurality of family members can be identified as molecularscaffolds. When the orientation of the scaffold at the binding site ofthe target molecules has been determined and chemically tractablestructures have been identified, a set of ligands can be synthesizedstarting with one or a few molecular scaffolds to arrive at a pluralityof ligands, wherein each ligand binds to a separate target molecule ofthe molecular family with altered or changed binding affinity or bindingspecificity relative to the scaffold. Thus, a plurality of drug leadmolecules can be designed to preferentially target individual members ofa molecular family based on the same molecular scaffold, and act on themin a specific manner.

IX. Binding Assays

The methods of the present invention can involve assays that are able todetect the binding of compounds to a target molecule. Such binding is ata statistically significant level, preferably with a confidence level ofat least 90%, more preferably at least 95, 97, 98, 99% or greaterconfidence level that the assay signal represents binding to the targetmolecule, i.e., is distinguished from background. Preferably controlsare used to distinguish target binding from non-specific binding. Theassays of the present invention can also include assaying compounds forlow affinity binding to the target molecule. A large variety of assaysindicative of binding are known for different target types and can beused for this invention. Compounds that act broadly across proteinfamilies are not likely to have a high affinity against individualtargets, due to the broad nature of their binding. Thus, assaysdescribed herein allow for the identification of compounds that bindwith low affinity, very low affinity, and extremely low affinity.Therefore, potency (or binding affinity) is not the primary, nor eventhe most important, indicia of identification of a potentially usefulbinding compound. Rather, even those compounds that bind with lowaffinity, very low affinity, or extremely low affinity can be consideredas molecular scaffolds that can continue to the next phase of the liganddesign process.

By binding with “low affinity” is meant binding to the target moleculewith a dissociation constant (k_(d)) of greater than 1 μM under standardconditions. By binding with “very low affinity” is meant binding with ak_(d) of above about 100 μM under standard conditions. By binding with“extremely low affinity” is meant binding at a k_(d) of above about 1 mMunder standard conditions. By “moderate affinity” is meant binding witha k_(d) of from about 200 nM to about 1 μM under standard conditions. By“moderately high affinity” is meant binding at a k_(d) of from about 1nM to about 200 nM. By binding at “high affinity” is meant binding at ak_(d) of below about 1 nM under standard conditions. For example, lowaffinity binding can occur because of a poorer fit into the binding siteof the target molecule or because of a smaller number of non-covalentbonds, or weaker covalent bonds present to cause binding of the scaffoldor ligand to the binding site of the target molecule relative toinstances where higher affinity binding occurs. The standard conditionsfor binding are at pH 7.2 at 37° C. for one hour. For example, 100μl/well can be used in HEPES 50 mM buffer at pH 7.2, NaCl 15 mM, ATP 2μM, and bovine serum albumin 1 μg/well, 37° C. for one hour.

Binding compounds can also be characterized by their effect on theactivity of the target molecule. Thus, a “low activity” compound has aninhibitory concentration (IC₅₀) or excitation concentration (EC₅₀) ofgreater than 1 μM under standard conditions. By “very low activity” ismeant an IC₅₀ or EC₅₀ of above 100 μM under standard conditions. By“extremely low activity” is meant an IC₅₀ or EC₅₀ of above 1 mM understandard conditions. By “moderate activity” is meant an IC₅₀ or EC₅₀ of200 nM to 1 μM under standard conditions. By “moderately high activity”is meant an IC₅₀ or EC₅₀ of 1 nM to 200 nM. By “high activity” is meantan IC₅₀ or EC₅₀ of below 1 nM under standard conditions. The IC₅₀ (orEC₅₀) is defined as the concentration of compound at which 50% of theactivity of the target molecule (e.g., enzyme or other protein) activitybeing measured is lost (or gained) relative to activity when no compoundis present. Activity can be measured using methods known to those ofordinary skill in the art, e.g. by measuring any detectable product orsignal produced by occurrence of an enzymatic reaction, or otheractivity by a protein being measured.

By “background signal” in reference to a binding assay is meant thesignal that is recorded under standard conditions for the particularassay in the absence of a test compound, molecular scaffold, or ligandthat binds to the target molecule. Persons of ordinary skill in the artwill realize that accepted methods exist and are widely available fordetermining background signal.

By “standard deviation” is meant the square root of the variance. Thevariance is a measure of how spread out a distribution is. It iscomputed as the average squared deviation of each number from its mean.For example, for the numbers 1, 2, and 3, the mean is 2 and the varianceis:

$\sigma^{2} = {\frac{\left( {1 - 2} \right)^{2} + \left( {2 - 2} \right)^{2} + \left( {3 - 2} \right)^{2}}{3} = {0.667.}}$

To design or discover scaffolds that act broadly across proteinfamilies, proteins of interest can be assayed against a compoundcollection or set. The assays can preferably be enzymatic or bindingassays. In some embodiments it may be desirable to enhance thesolubility of the compounds being screened and then analyze allcompounds that show activity in the assay, including those that bindwith low affinity or produce a signal with greater than about threetimes the standard deviation of the background signal. The assays can beany suitable assay such as, for example, binding assays that measure thebinding affinity between two binding partners. Various types ofscreening assays that can be useful in the practice of the presentinvention are known in the art, such as those described in U.S. Pat.Nos. 5,763,198, 5,747,276, 5,877,007, 6,243,980, 6,294,330, and6,294,330, each of which is hereby incorporated by reference in itsentirety, including all charts and drawings.

In various embodiments of the assays at least one compound, at leastabout 5%, at least about 10%, at least about 15%, at least about 20%, orat least about 25% of the compounds can bind with low affinity. Ingeneral, up to about 20% of the compounds can show activity in thescreening assay and these compounds can then be analyzed directly withhigh-throughput co-crystallography, computational analysis to group thecompounds into classes with common structural properties (e.g.,structural core and/or shape and polarity characteristics), and theidentification of common chemical structures between compounds that showactivity.

The person of ordinary skill in the art will realize that decisions canbe based on criteria that are appropriate for the needs of theparticular situation, and that the decisions can be made by computersoftware programs. Classes can be created containing almost any numberof scaffolds, and the criteria selected can be based on increasinglyexacting criteria until an arbitrary number of scaffolds is arrived atfor each class that is deemed to be advantageous.

Surface Plasmon Resonance

Binding parameters can be measured using surface plasmon resonance, forexample, with a BIAcore® chip (Biacore, Japan) coated with immobilizedbinding components. Surface plasmon resonance is used to characterizethe microscopic association and dissociation constants of reactionbetween an sFv or other ligand directed against target molecules. Suchmethods are generally described in the following references which areincorporated herein by reference. Vely F. et al., (2000) BIAcore®analysis to test phosphopeptide-SH2 domain interactions, Methods inMolecular Biology. 121:313-21; Liparoto et al., (1999) Biosensoranalysis of the interleukin-2 receptor complex, Journal of MolecularRecognition. 12:316-21; Lipschultz et al., (2000) Experimental designfor analysis of complex kinetics using surface plasmon resonance,Methods. 20:310-8; Malmqvist., (1999) BIACORE: an affinity biosensorsystem for characterization of biomolecular interactions, BiochemicalSociety Transactions 27:335-40; Alfthan, (1998) Surface plasmonresonance biosensors as a tool in antibody engineering, Biosensors &Bioelectronics. 13:653-63; Fivash et al., (1998) BIAcore formacromolecular interaction, Current Opinion in Biotechnology. 9:97-101;Price et al.; (1998) Summary report on the ISOBM TD-4 Workshop: analysisof 56 monoclonal antibodies against the MUC1 mucin. Tumour Biology 19Suppl 1:1-20; Malmqvist et al, (1997) Biomolecular interaction analysis:affinity biosensor technologies for functional analysis of proteins,Current Opinion in Chemical Biology. 1:378-83; O'Shannessy et al.,(1996) Interpretation of deviations from pseudo-first-order kineticbehavior in the characterization of ligand binding by biosensortechnology, Analytical Biochemistry. 236:275-83; Malmborg et al., (1995)BIAcore as a tool in antibody engineering, Journal of ImmunologicalMethods. 183:7-13; Van Regenmortel, (1994) Use of biosensors tocharacterize recombinant proteins, Developments in BiologicalStandardization. 83:143-51; and O'Shannessy, (1994) Determination ofkinetic rate and equilibrium binding constants for macromolecularinteractions: a critique of the surface plasmon resonance literature,Current Opinions in Biotechnology. 5:65-71.

BIAcore® uses the optical properties of surface plasmon resonance (SPR)to detect alterations in protein concentration bound to a dextran matrixlying on the surface of a gold/glass sensor chip interface, a dextranbiosensor matrix. In brief, proteins are covalently bound to the dextranmatrix at a known concentration and a ligand for the protein is injectedthrough the dextran matrix. Near infrared light, directed onto theopposite side of the sensor chip surface is reflected and also inducesan evanescent wave in the gold film, which in turn, causes an intensitydip in the reflected light at a particular angle known as the resonanceangle. If the refractive index of the sensor chip surface is altered(e.g., by ligand binding to the bound protein) a shift occurs in theresonance angle. This angle shift can be measured and is expressed asresonance units (RUs) such that 1000 RUs is equivalent to a change insurface protein concentration of 1 ng/mm². These changes are displayedwith respect to time along the y-axis of a sensorgram, which depicts theassociation and dissociation of any biological reaction.

High Throughput Screening (HTS) Assays

HTS typically uses automated assays to search through large numbers ofcompounds for a desired activity. Typically HTS assays are used to findnew drugs by screening for chemicals that act on a particular enzyme ormolecule. For example, if a chemical inactivates an enzyme it mightprove to be effective in preventing a process in a cell which causes adisease. High throughput methods enable researchers to assay thousandsof different chemicals against each target molecule very quickly usingrobotic handling systems and automated analysis of results.

As used herein, “high throughput screening” or “HTS” refers to the rapidin vitro screening of large numbers of compounds (libraries); generallytens to hundreds of thousands of compounds, using robotic screeningassays. Ultra high-throughput Screening (uHTS) generally refers to thehigh-throughput screening accelerated to greater than 100,000 tests perday.

To achieve high-throughput screening, it is advantageous to housesamples on a multicontainer carrier or platform. A multicontainercarrier facilitates measuring reactions of a plurality of candidatecompounds simultaneously. Multi-well microplates may be used as thecarrier. Such multi-well microplates, and methods for their use innumerous assays, are both known in the art and commercially available.

Screening assays may include controls for purposes of calibration andconfirmation of proper manipulation of the components of the assay.Blank wells that contain all of the reactants but no member of thechemical library are usually included. As another example, a knowninhibitor (or activator) of an enzyme for which modulators are sought,can be incubated with one sample of the assay, and the resultingdecrease (or increase) in the enzyme activity used as a comparator orcontrol. It will be appreciated that modulators can also be combinedwith the enzyme activators or inhibitors to find modulators whichinhibit the enzyme activation or repression that is otherwise caused bythe presence of the known the enzyme modulator. Similarly, when ligandsto a sphingolipid target are sought, known ligands of the target can bepresent in control/calibration assay wells.

Measuring Enzymatic and Binding Reactions During Screening Assays

Techniques for measuring the progression of enzymatic and bindingreactions, e.g., in multicontainer carriers, are known in the art andinclude, but are not limited to, the following.

Spectrophotometric and spectrofluorometric assays are well known in theart. Examples of such assays include the use of calorimetric assays forthe detection of peroxides, as described in Gordon, A. J. and Ford, R.A., (1972) The Chemist's Companion: A Handbook Of Practical Data,Techniques, And References, John Wiley and Sons, N.Y., Page 437.

Fluorescence spectrometry may be used to monitor the generation ofreaction products. Fluorescence methodology is generally more sensitivethan the absorption methodology. The use of fluorescent probes is wellknown to those skilled in the art. For reviews, see Bashford et al.,(1987) Spectrophotometry and Spectrofluorometry. A Practical Approach,pp. 91-114, IRL Press Ltd.; and Bell, (1981) Spectroscopy InBiochemistry, Vol. I, pp. 155-194, CRC Press.

In spectrofluorometric methods, enzymes are exposed to substrates thatchange their intrinsic fluorescence when processed by the target enzyme.Typically, the substrate is nonfluorescent and is converted to afluorophore through one or more reactions. As a non-limiting example,SMase activity can be detected using the Amplex® Red reagent (MolecularProbes, Eugene, Oreg.). In order to measure sphingomyelinase activityusing Amplex® Red, the following reactions occur. First, SMasehydrolyzes sphingomyelin to yield ceramide and phosphorylcholine.Second, alkaline phosphatase hydrolyzes phosphorylcholine to yieldcholine. Third, choline is oxidized by choline oxidase to betaine.Finally, H₂O₂, in the presence of horseradish peroxidase, reacts withAmplex® Red to produce the fluorescent product, Resorufin, and thesignal therefrom is detected using spectrofluorometry.

Fluorescence polarization (FP) is based on a decrease in the speed ofmolecular rotation of a fluorophore that occurs upon binding to a largermolecule, such as a receptor protein, allowing for polarized fluorescentemission by the bound ligand. FP is empirically determined by measuringthe vertical and horizontal components of fluorophore emission followingexcitation with plane polarized light. Polarized emission is increasedwhen the molecular rotation of a fluorophore is reduced. A fluorophoreproduces a larger polarized signal when it is bound to a larger molecule(i.e. a receptor), slowing molecular rotation of the fluorophore. Themagnitude of the polarized signal relates quantitatively to the extentof fluorescent ligand binding. Accordingly, polarization of the “bound”signal depends on maintenance of high affinity binding.

FP is a homogeneous technology and reactions are very rapid, takingseconds to minutes to reach equilibrium. The reagents are stable, andlarge batches may be prepared, resulting in high reproducibility.Because of these properties, FP has proven to be highly automatable,often performed with a single incubation with a single, premixed,tracer-receptor reagent. For a review, see Owicki et al., (1997),Application of Fluorescence Polarization Assays in High-ThroughputScreening, Genetic Engineering News, 17:27.

FP is particularly desirable since its readout is independent of theemission intensity (Checovich, W. J., et al., (1995) Nature 375:254-256;Dandliker, W. B., et al., (1981) Methods in Enzymology 74:3-28) and isthus insensitive to the presence of colored compounds that quenchfluorescence emission. FP and FRET (see below) are well-suited foridentifying compounds that block interactions between sphingolipidreceptors and their ligands. See, for example, Parker et al., (2000)Development of high throughput screening assays using fluorescencepolarization: nuclear receptor-ligand-binding and kinase/phosphataseassays, J Biomol Screen 5:77-88.

Fluorophores derived from sphingolipids that may be used in FP assaysare commercially available. For example, Molecular Probes (Eugene,Oreg.) currently sells sphingomyelin and one ceramide fluorophores.These are, respectively,N-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-pentanoyl)sphingosylphosphocholine (BODIPY® FL C5-sphingomyelin);N-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-dodecanoyl)sphingosylphosphocholine (BODIPY® FL C12-sphingomyelin); andN-(4,4-difluoro-5,7-dimethyl-4-bora-3a,4a-diaza-s-indacene-3-pentanoyl)sphingosine(BODIPY® FL C5-ceramide). U.S. Pat. No. 4,150,949, (Immunoassay forgentamicin), discloses fluorescein-labelled gentamicins, includingfluoresceinthiocarbanyl gentamicin. Additional fluorophores may beprepared using methods well known to the skilled artisan.

Exemplary normal-and-polarized fluorescence readers include thePOLARION® fluorescence polarization system (Tecan AG, Hombrechtikon,Switzerland). General multiwell plate readers for other assays areavailable, such as the VERSAMAX® reader and the SPECTRAMAX® multiwellplate spectrophotometer (both from Molecular Devices).

Fluorescence resonance energy transfer (FRET) is another useful assayfor detecting interaction and has been described. See, e.g., Heim etal., (1996) Curr. Biol. 6:178-182; Mitra et al., (1996) Gene 173:13-17;and Selvin et al., (1995) Meth. Enzymol. 246:300-345. FRET detects thetransfer of energy between two fluorescent substances in closeproximity, having known excitation and emission wavelengths. As anexample, a protein can be expressed as a fusion protein with greenfluorescent protein (GFP). When two fluorescent proteins are inproximity, such as when a protein specifically interacts with a targetmolecule, the resonance energy can be transferred from one excitedmolecule to the other. As a result, the emission spectrum of the sampleshifts, which can be measured by a fluorometer, such as a fMAX multiwellfluorometer (Molecular Devices, Sunnyvale Calif.).

Scintillation proximity assay (SPA) is a particularly useful assay fordetecting an interaction with the target molecule. SPA is widely used inthe pharmaceutical industry and has been described (Hanselman et al.,(1997) J. Lipid Res. 38:2365-2373; Kahl et al., (1996) Anal. Biochem.243:282-283; Undenfriend et al., (1987) Anal. Biochem. 161:494-500). Seealso U.S. Pat. Nos. 4,626,513 and 4,568,649, and European Patent No.0,154,734. One commercially available system uses FLASHPLATE®scintillant-coated plates (NEN Life Science Products, Boston, Mass.).

The target molecule can be bound to the scintillator plates by a varietyof well known means. Scintillant plates are available that arederivatized to bind to fusion proteins such as GST, His6 or Flag fusionproteins. Where the target molecule is a protein complex or a multimer,one protein or subunit can be attached to the plate first, then theother components of the complex added later under binding conditions,resulting in a bound complex.

In a typical SPA assay, the gene products in the expression pool willhave been radiolabeled and added to the wells, and allowed to interactwith the solid phase, which is the immobilized target molecule andscintillant coating in the wells. The assay can be measured immediatelyor allowed to reach equilibrium. Either way, when a radiolabel becomessufficiently close to the scintillant coating, it produces a signaldetectable by a device such as a TOPCOUNT NXT® microplate scintillationcounter (Packard BioScience Co., Meriden Conn.). If a radiolabeledexpression product binds to the target molecule, the radiolabel remainsin proximity to the scintillant long enough to produce a detectablesignal.

In contrast, the labeled proteins that do not bind to the targetmolecule, or bind only briefly, will not remain near the scintillantlong enough to produce a signal above background. Any time spent nearthe scintillant caused by random Brownian motion will also not result ina significant amount of signal. Likewise, residual unincorporatedradiolabel used during the expression step may be present, but will notgenerate significant signal because it will be in solution rather thaninteracting with the target molecule. These non-binding interactionswill therefore cause a certain level of background signal that can bemathematically removed. If too many signals are obtained, salt or othermodifiers can be added directly to the assay plates until the desiredspecificity is obtained (Nichols et al., (1998) Anal. Biochem.257:112-119).

Assay Compounds and Molecular Scaffolds

Preferred characteristics of a scaffold include being of low molecularweight (e.g., less than 350 Da, or from about 100 to about 350 daltons,or from about 150 to about 300 daltons). Preferably clog P of a scaffoldis from 1 to 8, more preferably less than 6, 5, or 4, most preferablyless than 3. In particular embodiments the clogP is in a range −1 to anupper limit of 2, 3, 4, 5, 6, or 8; or is in a range of 0 to an upperlimit of 2, 3, 4, 5, 6, or 8. Preferably the number of rotatable bondsis less than 5, more preferably less than 4. Preferably the number ofhydrogen bond donors and acceptors is below 6, more preferably below 5.An additional criterion that can be useful is a polar surface area ofless than 5. Guidance that can be useful in identifying criteria for aparticular application can be found in Lipinski et al., (1997) AdvancedDrag Delivery Reviews 23 3-25, which is hereby incorporated by referencein its entirety.

A scaffold may preferably bind to a given protein binding site in aconfiguration that causes substituent moieties of the scaffold to besituated in pockets of the protein binding site. Also, possessingchemically tractable groups that can be chemically modified,particularly through synthetic reactions, to easily create acombinatorial library can be a preferred characteristic of the scaffold.Also preferred can be having positions on the scaffold to which othermoieties can be attached, which do not interfere with binding of thescaffold to the protein(s) of interest but do cause the scaffold toachieve a desirable property, for example, active transport of thescaffold to cells and/or organs, enabling the scaffold to be attached toa chromatographic column to facilitate analysis, or another desirableproperty. A molecular scaffold can bind to a target molecule with anyaffinity, such as binding at high affinity, moderate affinity, lowaffinity, very low affinity, or extremely low affinity.

Thus, the above criteria can be utilized to select many compounds fortesting that have the desired attributes. Many compounds having thecriteria described are available in the commercial market, and may beselected for assaying depending on the specific needs to which themethods are to be applied.

A “compound library” or “library” is a collection of different compoundshaving different chemical structures. A compound library is screenable,that is, the compound library members therein may be subject toscreening assays. In preferred embodiments, the library members can havea molecular weight of from about 100 to about 350 daltons, or from about150 to about 350 daltons. Examples of libraries are provided above.

Libraries of the present invention can contain at least one compoundthan binds to the target molecule at low affinity. Libraries ofcandidate compounds can be assayed by many different assays, such asthose described above, e.g., a fluorescence polarization assay.Libraries may consist of chemically synthesized peptides,peptidomimetics, or arrays of combinatorial chemicals that are large orsmall, focused or nonfocused. By “focused” it is meant that thecollection of compounds is prepared using the structure of previouslycharacterized compounds and/or pharmacophores.

Compound libraries may contain molecules isolated from natural sources,artificially synthesized molecules, or molecules synthesized, isolated,or otherwise prepared in such a manner so as to have one or moremoieties variable, e.g., moieties that are independently isolated orrandomly synthesized. Types of molecules in compound libraries includebut are not limited to organic compounds, polypeptides and nucleic acidsas those terms are used herein, and derivatives, conjugates and mixturesthereof.

Compound libraries of the invention may be purchased on the commercialmarket or prepared or obtained by any means including, but not limitedto, combinatorial chemistry techniques, fermentation methods, plant andcellular extraction procedures and the like (see, e.g., Cwirla et al.,(1990) Biochemistry, 87, 6378-6382; Houghten et al., (1991) Nature, 354,84-86; Lam et al., (1991) Nature, 354, 82-84; Brenner et al., (1992)Proc. Natl. Acad. Sci. USA, 89, 5381-5383; R. A. Houghten, (1993) TrendsGenet., 9, 235-239; E. R. Felder, (1994) Chimia, 48, 512-541; Gallop etal., (1994) J. Med. Chem., 37, 1233-1251; Gordon et al., (1994) J. Med.Chem., 37, 1385-1401; Carell et al., (1995) Chem. Biol., 3, 171-183;Madden et al., Perspectives in Drug Discovery and Design 2, 269-282;Lebl et al., (1995) Biopolymers, 37 177-198); small molecules assembledaround a shared molecular structure; collections of chemicals that havebeen assembled by various commercial and noncommercial groups, naturalproducts; extracts of marine organisms, fungi, bacteria, and plants.

Preferred libraries can be prepared in a homogenous reaction mixture,and separation of unreacted reagents from members of the library is notrequired prior to screening. Although many combinatorial chemistryapproaches are based on solid state chemistry, liquid phasecombinatorial chemistry is capable of generating libraries (Sun C M.,(1999) Recent advances in liquid-phase combinatorial chemistry,Combinatorial Chemistry & High Throughput Screening. 2:299-318).

Libraries of a variety of types of molecules are prepared in order toobtain members therefrom having one or more preselected attributes thatcan be prepared by a variety of techniques, including but not limited toparallel array synthesis (Houghton, (2000) Annu Rev Pharmacol Toxicol40:273-82, Parallel array and mixture-based synthetic combinatorialchemistry; solution-phase combinatorial chemistry (Merritt, (1998) CombChem High Throughput Screen 1:57-72, Solution phase combinatorialchemistry, Coe et al., (1998-99) Mol. Divers. 4:31-8, Solution-phasecombinatorial chemistry, Sun, (1999) Comb Chem High Throughput Screen2:299-318, Recent advances in liquid-phase combinatorial chemistry);synthesis on soluble polymer (Gravert et al., (1997) Curr Opin Chem Biol1:107-13, Synthesis on soluble polymers: new reactions and theconstruction of small molecules); and the like. See, e.g., Dolle et al.,(1999) J Comb Chem 1:235-82, Comprehensive survey of combinatoriallibrary synthesis: 1998. Freidinger R M., (1999) Nonpeptidic ligands forpeptide and protein receptors, Current Opinion in Chemical Biology; andKundu et al., Prog Drug Res; 53:89-156, Combinatorial chemistry: polymersupported synthesis of peptide and non-peptide libraries). Compounds maybe clinically tagged for ease of identification (Chabala, (1995) CurrOpin Biotechnol 6:633-9, Solid-phase combinatorial chemistry and noveltagging methods for identifying leads).

The combinatorial synthesis of carbohydrates and libraries containingoligosaccharides have been described (Schweizer et al., (1999) Curr OpinChem. Biol. 3:291-8, Combinatorial synthesis of carbohydrates). Thesynthesis of natural-product based compound libraries has been described(Wessjohann, (2000) Curr Opin Chem Biol 4:303-9, Synthesis ofnatural-product based compound libraries).

Libraries of nucleic acids are prepared by various techniques, includingby way of non-limiting example the ones described herein, for theisolation of aptamers. Libraries that include oligonucleotides andpolyaminooligonucleotides (Markiewicz et al., (2000) Syntheticoligonucleotide combinatorial libraries and their applications, Farmaco.55:174-7) displayed on streptavidin magnetic beads are known. Nucleicacid libraries are known that can be coupled to parallel sampling and bedeconvoluted without complex procedures such as automated massspectrometry (Enjalbal C. Martinez J. Aubagnac J L, (2000) Massspectrometry in combinatorial chemistry, Mass Spectrometry Reviews.19:139-61) and parallel tagging. (Perrin D M., Nucleic acids forrecognition and catalysis: landmarks, limitations, and looking to thefuture, Combinatorial Chemistry & High Throughput Screening 3:243-69).

Peptidomimetics are identified using combinatorial chemistry and solidphase synthesis (Kim H O. Kahn M., (2000) A merger of rational drugdesign and combinatorial chemistry: development and application ofpeptide secondary structure mimetics, Combinatorial Chemistry & HighThroughput Screening 3:167-83; al-Obeidi, (1998) Mol Biotechnol9:205-23, Peptide and peptidomimetric libraries. Molecular diversity anddrug design). The synthesis may be entirely random or based in part on aknown polypeptide.

Polypeptide libraries can be prepared according to various techniques.In brief, phage display techniques can be used to produce polypeptideligands (Gram H., (1999) Phage display in proteolysis and signaltransduction, Combinatorial Chemistry & High Throughput Screening.2:19-28) that may be used as the basis for synthesis of peptidomimetics.Polypeptides, constrained peptides, proteins, protein domains,antibodies, single chain antibody fragments, antibody fragments, andantibody combining regions are displayed on filamentous phage forselection.

Large libraries of individual variants of human single chain Fvantibodies have been produced. See, e.g., Siegel R W. Allen B. Pavlik P.Marks J D. Bradbury A., (2000) Mass spectral analysis of a proteincomplex using single-chain antibodies selected on a peptide target:applications to functional genomics, Journal of Molecular Biology302:285-93; Poul M A. Becerril B. Nielsen U B. Morisson P. Marks J D.,(2000) Selection of tumor-specific internalizing human antibodies fromphage libraries. Source Journal of Molecular Biology. 301:1149-61;Amersdorfer P. Marks J D., (2001) Phage libraries for generation ofanti-botulinum scFv antibodies, Methods in Molecular Biology.145:219-40; Hughes-Jones N C. Bye J M. Gorick B D. Marks J D. Ouwehand WH., (1999) Synthesis of Rh Fv phage-antibodies using VH and VL germlinegenes, British Journal of Haematology. 105:811-6; McCall A M. Amoroso AR. Sautes C. Marks J D. Weiner L M., (1998) Characterization ofanti-mouse Fc gamma Rh single-chain Fv fragments derived from humanphage display libraries, Immunotechnology. 4:71-87; Sheets M D.Amersdorfer P. Finnern R. Sargent P. Lindquist E. Schier R. Hemingsen G.Wong C. Gerhart J C. Marks J D. Lindquist E., (1998) Efficientconstruction of a large nonimmune phage antibody library: the productionof high-affinity human single-chain antibodies to protein antigens(published erratum appears in Proc Natl Acad Sci USA 96:795), Proc NatlAcad Sci USA 95:6157-62).

Focused or smart chemical and pharmacophore libraries can be designedwith the help of sophisticated strategies involving computationalchemistry (e.g., Kundu B. Khare S K. Rastogi S K., (1999) Combinatorialchemistry: polymer supported synthesis of peptide and non-peptidelibraries, Progress in Drug Research 53:89-156) and the use ofstructure-based ligands using database searching and docking, de novodrug design and estimation of ligand binding affinities (Joseph-McCarthyD., (1999) Computational approaches to structure-based ligand design,Pharmacology & Therapeutics 84:179-91; Kirkpatrick D L. Watson S. UlhaqS., (1999) Structure-based drug design: combinatorial chemistry andmolecular modeling, Combinatorial Chemistry & High Throughput Screening.2:211-21; Eliseev A V. Lehn J M., (1999) Dynamic combinatorialchemistry: evolutionary formation and screening of molecular libraries,Current Topics in Microbiology & Immunology 243:159-72; Bolger et al.,(1991) Methods Enz. 203:21-45; Martin, (1991) Methods Enz. 203:587-613;Neidle et al., (1991) Methods Enz. 203:433-458; U.S. Pat. No.6,178,384).

X. Crystallography

After binding compounds have been determined, the orientation ofcompound bound to target is determined. Preferably this determinationinvolves crystallography on co-crystals of molecular scaffold compoundswith target. Most protein crystallographic platforms can preferably bedesigned to analyze up to about 500 co-complexes of compounds, ligands,or molecular scaffolds bound to protein targets due to the physicalparameters of the instruments and convenience of operation. If thenumber of scaffolds that have binding activity exceeds a numberconvenient for the application of crystallography methods, the scaffoldscan be placed into groups based on having at least one common chemicalstructure or other desirable characteristics, and representativecompounds can be selected from one or more of the classes. Classes canbe made with increasingly exacting criteria until a desired number ofclasses (e.g., 500) is obtained. The classes can be based on chemicalstructure similarities between molecular scaffolds in the class, e.g.,all possess a pyrrole ring, benzene ring, or other chemical feature.Likewise, classes can be based on shape characteristics, e.g.,space-filling characteristics.

The co-crystallography analysis can be performed by co-complexing eachscaffold with its target at concentrations of the scaffold that showedactivity in the screening assay. This co-complexing can be accomplishedwith the use of low percentage organic solvents with the target moleculeand then concentrating the target with each of the scaffolds. Inpreferred embodiments these solvents are less than 5% organic solventsuch as dimethyl sulfoxide (DMSO), ethanol, methanol, or ethylene glycolin water or another aqueous solvent. Each scaffold complexed to thetarget molecule can then be screened with a suitable number ofcrystallization screening conditions at both 4 and 20 degrees. Inpreferred embodiments, about 96 crystallization screening conditions canbe performed in order to obtain sufficient information about theco-complexation and crystallization conditions, and the orientation ofthe scaffold at the binding site of the target molecule. Crystalstructures can then be analyzed to determine how the bound scaffold isoriented physically within the binding site or within one or morebinding pockets of the molecular family member.

It is desirable to determine the atomic coordinates of the compoundsbound to the target proteins in order to determine which is a mostsuitable scaffold for the protein family. X-ray crystallographicanalysis is therefore most preferable for determining the atomiccoordinates. Those compounds selected can be further tested with theapplication of medicinal chemistry. Compounds can be selected formedicinal chemistry testing based on their binding position in thetarget molecule. For example, when the compound binds at a binding site,the compound's binding position in the binding site of the targetmolecule can be considered with respect to the chemistry that can beperformed on chemically tractable structures or sub-structures of thecompound, and how such modifications on the compound might interact withstructures or sub-structures on the binding site of the target. Thus,one can explore the binding site of the target and the chemistry of thescaffold in order to make decisions on how to modify the scaffold toarrive at a ligand with higher potency and/or selectivity. This processallows for more direct design of ligands, by utilizing structural andchemical information obtained directly from the co-complex, therebyenabling one to more efficiently and quickly design lead compounds thatare likely to lead to beneficial drug products. In various embodimentsit may be desirable to perform co-crystallography on all scaffolds thatbind, or only those that bind with a particular affinity, for example,only those that bind with high affinity, moderate affinity, lowaffinity, very low affinity, or extremely low affinity. It may also beadvantageous to perform co-crystallography on a selection of scaffoldsthat bind with any combination of affinities.

Standard X-ray protein diffraction studies such as by using a RigakuRU-200® (Rigaku, Tokyo, Japan) with an X-ray imaging plate detector or asynchrotron beam-line can be performed on co-crystals and thediffraction data measured on a standard X-ray detector, such as a CCDdetector or an X-ray imaging plate detector.

Performing X-ray crystallography on about 200 co-crystals shouldgenerally lead to about 50 co-crystals structures, which should provideabout 10 scaffolds for validation in chemistry, which should finallyresult in about 5 selective leads for target molecules.

Virtual Assays

Commercially available software that generates three-dimensionalgraphical representations of the complexed target and compound from aset of coordinates provided can be used to illustrate and study how acompound is oriented when bound to a target. (e.g., QUANTA®, Accelerys,San Diego, Calif.). Thus, the existence of binding pockets at thebinding site of the targets can be particularly useful in the presentinvention. These binding pockets are revealed by the crystallographicstructure determination and show the precise chemical interactionsinvolved in binding the compound to the binding site of the target. Theperson of ordinary skill will realize that the illustrations can also beused to decide where chemical groups might be added, substituted,modified, or deleted from the scaffold to enhance binding or anotherdesirable effect, by considering where unoccupied space is located inthe complex and which chemical substructures might have suitable sizeand/or charge characteristics to fill it. The person of ordinary skillwill also realize that regions within the binding site can be flexibleand its properties can change as a result of scaffold binding, and thatchemical groups can be specifically targeted to those regions to achievea desired effect. Specific locations on the molecular scaffold can beconsidered with reference to where a suitable chemical substructure canbe attached and in which conformation, and which site has the mostadvantageous chemistry available.

An understanding of the forces that bind the compounds to the targetproteins reveals which compounds can most advantageously be used asscaffolds, and which properties can most effectively be manipulated inthe design of ligands. The person of ordinary skill will realize thatsteric, ionic, hydrogen bond, and other forces can be considered fortheir contribution to the maintenance or enhancement of thetarget-compound complex. Additional data can be obtained with automatedcomputational methods, such as docking and/or Free Energy Perturbations(FEP), to account for other energetic effects such as desolvationpenalties. The compounds selected can be used to generate informationabout the chemical interactions with the target or for elucidatingchemical modifications that can enhance selectivity of binding of thecompound.

Computer models, such as homology models (i.e., based on a known,experimentally derived structure) can be constructed using data from theco-crystal structures. When the target molecule is a protein or enzyme,preferred co-crystal structures for making homology models contain highsequence identity in the binding site of the protein sequence beingmodeled, and the proteins will preferentially also be within the sameclass and/or fold family. Knowledge of conserved residues in activesites of a protein class can be used to select homology models thataccurately represent the binding site. Homology models can also be usedto map structural information from a surrogate protein where an apo orco-crystal structure exists to the target protein.

Virtual screening methods, such as docking, can also be used to predictthe binding configuration and affinity of scaffolds, compounds, and/orcombinatorial library members to homology models. Using this data, andcarrying out “virtual experiments” using computer software can savesubstantial resources and allow the person of ordinary skill to makedecisions about which compounds can be suitable scaffolds or ligands,without having to actually synthesize the ligand and performco-crystallization. Decisions thus can be made about which compoundsmerit actual synthesis and co-crystallization. An understanding of suchchemical interactions aids in the discovery and design of drugs thatinteract more advantageously with target proteins and/or are moreselective for one protein family member over others. Thus, applyingthese principles, compounds with superior properties can be discovered.

Additives that promote co-crystallization can of course be included inthe target molecule formulation in order to enhance the formation ofco-crystals. In the case of proteins or enzymes, the scaffold to betested can be added to the protein formulation, which is preferablypresent at a concentration of approximately 1 mg/ml. The formulation canalso contain between 0%-10% (v/v) organic solvent, e.g. DMSO, methanol,ethanol, propane diol, or 1,3 dimethyl propane diol (MPD) or somecombination of those organic solvents. Compounds are preferablysolubilized in the organic solvent at a concentration of about 10 mM andadded to the protein sample at a concentration of about 100 mM. Theprotein-compound complex is then concentrated to a final concentrationof protein of from about 5 to about 20 mg/ml. The complexation andconcentration steps can conveniently be performed using a 96-wellformatted concentration apparatus (e.g., Amicon Inc., Piscataway, N.J.).Buffers and other reagents present in the formulation being crystallizedcan contain other components that promote crystallization or arecompatible with crystallization conditions, such as DTT, propane diol,glycerol.

The crystallization experiment can be set-up by placing small aliquotsof the concentrated protein-compound complex (1 μl) in a 96 well formatand sampling under 96 crystallization conditions. (Other screeningformats can also be used, e.g., plates with greater than 96 wells.)Crystals can typically be obtained using standard crystallizationprotocols that can involve the 96 well crystallization plate beingplaced at different temperatures. Co-crystallization varying factorsother than temperature can also be considered for each protein-compoundcomplex if desirable. For example, atmospheric pressure, the presence orabsence of light or oxygen, a change in gravity, and many othervariables can all be tested. The person of ordinary skill in the artwill realize other variables that can advantageously be varied andconsidered.

Ligand Design and Preparation

The design and preparation of ligands can be performed with or withoutstructural and/or co-crystallization data by considering the chemicalstructures in common between the active scaffolds of a set. In thisprocess structure-activity hypotheses can be formed and those chemicalstructures found to be present in a substantial number of the scaffolds,including those that bind with low affinity, can be presumed to havesome effect on the binding of the scaffold. This binding can be presumedto induce a desired biochemical effect when it occurs in a biologicalsystem (e.g., a treated mammal). New or modified scaffolds orcombinatorial libraries derived from scaffolds can be tested to disprovethe maximum number of binding and/or structure-activity hypotheses. Theremaining hypotheses can then be used to design ligands that achieve adesired binding and biochemical effect.

But in many cases it will be preferred to have co-crystallography datafor consideration of how to modify the scaffold to achieve the desiredbinding effect (e.g., binding at higher affinity or with higherselectivity). Using the case of proteins and enzymes, co-crystallographydata shows the binding pocket of the protein with the molecular scaffoldbound to the binding site, and it will be apparent that a modificationcan be made to a chemically tractable group on the scaffold. Forexample, a small volume of space at a protein binding site or pocketmight be filled by modifying the scaffold to include a small chemicalgroup that fills the volume. Filling the void volume can be expected toresult in a greater binding affinity, or the loss of undesirable bindingto another member of the protein family. Similarly, theco-crystallography data may show that deletion of a chemical group onthe scaffold may decrease a hindrance to binding and result in greaterbinding affinity or specificity.

It can be desirable to take advantage of the presence of a chargedchemical group located at the binding site or pocket of the protein. Forexample, a positively charged group can be complemented with anegatively charged group introduced on the molecular scaffold. This canbe expected to increase binding affinity or binding specificity, therebyresulting in a more desirable ligand. In many cases, regions of proteinbinding sites or pockets are known to vary from one family member toanother based on the amino acid differences in those regions. Chemicaladditions in such regions can result in the creation or elimination ofcertain interactions (e.g., hydrophobic, electrostatic, or entropic)that allow a compound to be more specific for one protein target overanother or to bind with greater affinity, thereby enabling one tosynthesize a compound with greater selectivity or affinity for aparticular family member. Additionally, certain regions can containamino acids that are known to be more flexible than others. This oftenoccurs in amino acids contained in loops connecting elements of thesecondary structure of the protein, such as alpha helices or betastrands. Additions of chemical moieties can also be directed to theseflexible regions in order to increase the likelihood of a specificinteraction occurring between the protein target of interest and thecompound. Virtual screening methods can also be conducted in silico toassess the effect of chemical additions, subtractions, modifications,and/or substitutions on compounds with respect to members of a proteinfamily or class.

The addition, subtraction, or modification of a chemical structure orsub-structure to a scaffold can be performed with any suitable chemicalmoiety. For example the following moieties, which are provided by way ofexample and are not intended to be limiting, can be utilized: hydrogen,alkyl, alkoxy, phenoxy, alkenyl, alkynyl, phenylalkyl, hydroxyalkyl,haloalkyl, aryl, arylalkyl, alkyloxy, alkylthio, alkenylthio, phenyl,phenylalkyl, phenylalkylthio, hydroxyalkyl-thio, alkylthiocarbbamylthio,cyclohexyl, pyridyl, piperidinyl, alkylamino, amino, nitro, mercapto,cyano, hydroxyl, a halogen atom, halomethyl, an oxygen atom (e.g.,forming a ketone or N-oxide) or a sulphur atom (e.g., forming a thiol,thione, di-alkylsulfoxide or sulfone) are all examples of moieties thatcan be utilized.

Additional examples of structures or sub-structures that may be utilizedare an aryl optionally substituted with one, two, or three substituentsindependently selected from the group consisting of alkyl, alkoxy,halogen, trihalomethyl, carboxylate, carboxamide, nitro, and estermoieties; an amine of formula —NX₂X₃, where X₂ and X₃ are independentlyselected from the group consisting of hydrogen, saturated or unsaturatedalkyl, and homocyclic or heterocyclic ring moieties; halogen ortrihalomethyl; a ketone of formula —COX₄, where X₄ is selected from thegroup consisting of alkyl and homocyclic or heterocyclic ring moieties;a carboxylic acid of formula —(X₅)_(n)COOH or ester of formula(X₆)_(n)COOX₇, where X₅, X₆, and X₇ and are independently selected fromthe group consisting of alkyl and homocyclic or heterocyclic ringmoieties and where n is 0 or 1; an alcohol of formula (X₈)_(n)OH or analkoxy moiety of formula —(X₈)_(n)OX₉, where X₈ and X₉ are independentlyselected from the group consisting of saturated or unsaturated alkyl andhomocyclic or heterocyclic ring moieties, wherein said ring isoptionally substituted with one or more substituents independentlyselected from the group consisting of alkyl, alkoxy, halogen,trihalomethyl, carboxylate, nitro, and ester and where n is 0 or 1; anamide of formula NHCOX₁₀, where X₁₀ is selected from the groupconsisting of alkyl, hydroxyl, and homocyclic or heterocyclic ringmoieties, wherein said ring is optionally substituted with one or moresubstituents independently selected from the group consisting of alkyl,alkoxy, halogen, trihalomethyl, carboxylate, nitro, and ester; SO₂,NX₁₁X₁₂, where X₁₁ and X₁₂ are selected from the group consisting ofhydrogen, alkyl, and homocyclic or heterocyclic ring moieties; ahomocyclic or heterocyclic ring moiety optionally substituted with one,two, or three substituents independently selected from the groupconsisting of alkyl, alkoxy, halogen, trihalomethyl, carboxylate,carboxamide, nitro, and ester moieties; an aldehyde of formula —CHO; asulfone of formula —SO₂X₁₃, where X₁₃ is selected from the groupconsisting of saturated or unsaturated alkyl and homocyclic orheterocyclic ring moieties; and a nitro of formula —NO₂.

Identification of Attachment Sites on Molecular Scaffolds and Ligands

In addition to the identification and development of ligands for kinasesand other enzymes, determination of the orientation of a molecularscaffold or other binding compound in a binding site allowsidentification of energetically allowed sites for attachment of thebinding molecule to another component. For such sites, any free energychange associated with the presence of the attached component should notdestabilize the binding of the compound to the kinase to an extent thatwill disrupt the binding. Preferably, the binding energy with theattachment should be at least 4 kcal/mol., more preferably at least 6,8, 10, 12, 15, or 20 kcal/mol. Preferably, the presence of theattachment at the particular site reduces binding energy by no more than3, 4, 5, 8, 10, 12, or 15 kcal/mol.

In many cases, suitable attachment sites will be those that are exposedto solvent when the binding compound is bound in the binding site. Insome cases, attachment sites can be used that will result in smalldisplacements of a portion of the enzyme without an excessive energeticcost. Exposed sites can be identified in various ways. For example,exposed sites can be identified using a graphic display or 3-dimensionalmodel. In a graphic display, such as a computer display, an image of acompound bound in a binding site can be visually inspected to revealatoms or groups on the compound that are exposed to solvent and orientedsuch that attachment at such atom or group would not preclude binding ofthe enzyme and binding compound. Energetic costs of attachment can becalculated based on changes or distortions that would be caused by theattachment as well as entropic changes.

Many different types of components can be attached. Persons with skillare familiar with the chemistries used for various attachments. Examplesof components that can be attached include, without limitation: solidphase components such as beads, plates, chips, and wells; a direct orindirect label; a linker, which may be a traceless linker; among others.Such linkers can themselves be attached to other components, e.g., tosolid phase media, labels, and/or binding moieties.

The binding energy of a compound and the effects on binding energy forattaching the molecule to another component can be calculatedapproximately using any of a variety of available software or by manualcalculation. An example is the following:

Calculations were performed to estimate binding energies of differentorganic molecules to c-kit. The organic molecules considered includedGleevec, identified compounds that bind to c-kit, and several linkers.

Calculated binding energies between protein-ligand complexes wereobtained using the FlexX score (an implementation of the Bohm scoringfunction) within the Tripos software suite. The form for that equationis shown in the equation below:ΔG _(bind) =ΔG _(tr) +ΔG _(hb) +ΔG _(ion) +ΔG _(lipo) +ΔG _(arom) +ΔG_(rot)

where: ΔG_(tr) is a constant term that accounts for the overall loss ofrotational and translational entropy of the ligand, ΔG_(hb) accounts forhydrogen bonds formed between the ligand and protein, ΔG_(ion) accountsfor the ionic interactions between the ligand and protein, ΔG_(lipo)accounts for the lipophilic interaction that corresponds to theprotein-ligand contact surface, ΔG_(arom) accounts for interactionsbetween aromatic rings in the protein and ligand, and ΔG_(rot) accountsfor the entropic penalty of restricting rotatable bonds in the ligandupon binding.

This method estimates the free energy that a lead compound should haveto a target protein for which there is a crystal structure, and itaccounts for the entropic penalty of flexible linkers. It can thereforebe used to estimate the free energy penalty incurred by attachinglinkers to molecules being screened and the binding energy that a leadcompound should have in order to overcome the free energy penalty of thelinker. The method does not account for salvation and the entropicpenalty is likely overestimated for cases where the linker is bound to asolid phase through another binding complex, such as abiotin:streptavidin complex.

Co-crystals were aligned by superimposing residues of c-Kit withcorresponding residues in FLT-3. Hydrogen atoms were added to theproteins and atomic charges were assigned using the AMBER95 parameterswithin Sybyl. Modifications to the compounds described were made withinthe Sybyl modeling suite from Tripos.

These calculations indicate that the calculated binding energy forcompounds that bind strongly to a given target can be lower than −25kcal/mol, while the calculated binding affinity for a good scaffold oran unoptimized binding compound can be in the range of −15 to −20. Thefree energy penalty for attachment to a linker such as the ethyleneglycol or hexatriene is estimated as typically being in the range of +5to +15 kcal/mol.

Linkers

Linkers suitable for use in the invention can be of many differenttypes. Linkers can be selected for particular applications based onfactors such as linker chemistry compatible for attachment to a bindingcompound and to another component utilized in the particularapplication. Additional factors can include, without limitation, linkerlength, linker stability, and ability to remove the linker at anappropriate time. Exemplary linkers include, but are not limited to,hexyl, hexatrienyl, ethylene glycol, and peptide linkers. Tracelesslinkers can also be used, e.g., as described in Plunkett, M. J., andEllman, J. A., (1995), J. Org. Chem., 60:6006.

Typical functional groups, that are utilized to link bindingcompound(s), include, but not limited to, carboxylic acid, amine,hydroxyl, and thiol. (Examples can be found in Solid-supportedcombinatorial and parallel synthesis of small molecular weight compoundlibraries; (1998) Tetrahedron organic chemistry series Vol. 17;Pergamon; p85).

Labels

As indicated above, labels can also be attached to a binding compound orto a linker attached to a binding compound. Such attachment may bedirect (attached directly to the binding compound) or indirect (attachedto a component that is directly or indirectly attached to the bindingcompound). Such labels allow detection of the compound either directlyor indirectly. Attachement of labels can be performed using conventionalchemistries. Labels can include, for example, fluorescent labels,radiolabels, light scattering particles, light absorbent particles,magnetic particles, enzymes, and specific binding agents (e.g., biotinor an antibody target moiety).

Solid Phase Media

Additional examples of components that can be attached directly orindirectly to a binding compound include various solid phase media.Similar to attachment of linkers and labels, attachment to solid phasemedia can be performed using conventional chemistries. Such solid phasemedia can include, for example, small components such as beads,nanoparticles, and fibers (e.g., in suspension or in a gel orchromatographic matrix). Likewise, solid phase media can include largerobjects such as plates, chips, slides, and tubes. In many cases, thebinding compound will be attached in only a portion of such an objects,e.g., in a spot or other local element on a generally flat surface or ina well or portion of a well.

Identification of Biological Agents

The possession of structural information about a protein also providesfor the identification of useful biological agents, such as epitopes fordevelopment of antibodies, identification of mutation sites expected toaffect activity, and identification of attachment sites allowingattachment of the protein to materials such as labels, linkers,peptides, and solid phase media.

Antibodies (Abs) finds multiple applications in a variety of areasincluding biotechnology, medicine and diagnosis, and indeed they are oneof the most powerful tools for life science research. Abs directedagainst protein antigens can recognize either linear or nativethree-dimensional (3D) epitopes. The obtention of Abs that recognize 3Depitopes require the use of whole native protein (or of a portion thatassumes a native conformation) as immunogens. Unfortunately, this notalways a choice due to various technical reasons: for example the nativeprotein is just not available, the protein is toxic, or its is desirableto utilize a high density antigen presentation. In such cases,immunization with peptides is the alternative. Of course, Abs generatedin this manner will recognize linear epitopes, and they might or mightnot recognize the source native protein, but yet they will be useful forstandard laboratory applications such as western blots. The selection ofpeptides to use as immunogens can be accomplished by followingparticular selection rules and/or use of epitope prediction software.

Though methods to predict antigenic peptides are not infallible, thereare several rules that can be followed to determine what peptidefragments from a protein are likely to be antigenic. These rules arealso dictated to increase the likelihood that an Ab to a particularpeptide will recognize the native protein.

-   -   1. Antigenic peptides should be located in solvent accessible        regions and contain both hydrophobic and hydrophilic residues.        -   For proteins of known 3D structure, solvent accessibility            can be determined using a variety of programs such as DSSP,            NACESS, or WHATIF, among others.        -   If the 3D structure is not known, use any of the following            web servers to predict accessibilities: PHD, JPRED,            PredAcc (c) ACCpro    -   2. Preferably select peptides lying in long loops connecting        Secondary Structure (SS) motifs, avoiding peptides located in        helical regions. This will increase the odds that the Ab        recognizes the native protein. Such peptides can, for example,        be identified from a crystal structure or crystal        structure-based homology model.        -   For protein with known 3D coordinates, SS can be obtained            from the sequence link of the relevant entry at the            Brookhaven data bank. The PDBsum server also offer SS            analysis of pdb records.        -   When no structure is available secondary structure            predictions can be obtained from any of the following            servers: PHD, JPRED, PSI-PRED, NNSP, etc    -   3. When possible, choose peptides that are in the N- and        C-terminal region of the protein. Because the N- and C-terminal        regions of proteins are usually solvent accessible and        unstructured, Abs against those regions are also likely to        recognize the native protein.    -   4. For cell surface glycoproteins, eliminate from initial        peptides those containing consensus sites for N-glycosilation.        -   N-glycosilation sites can be detected using Scanprosite, or            NetNGlyc

In addition, several methods based on various physio-chemical propertiesof experimental determined epitopes (flexibility, hydrophibility,accessibility) have been published for the prediction of antigenicdeterminants and can be used. The antigenic index and Preditop areexample.

Perhaps the simplest method for the prediction of antigenic determinantsis that of Kolaskar and Tongaonkar, which is based on the occurrence ofamino acid residues in experimentally determined epitopes. (Kolaskar andTongaonkar (1990) A semi-empirical method for prediction of antigenicdeterminants on protein antigens. FEBBS Lett. 276:172-174.) Theprediction algorithm works as follows:

-   -   1. Calculate the average propensity for each overlapping 7-mer        and assign the result to the central residue (i+3) of the 7-mer.    -   2. Calculate the average for the whole protein.    -   3. (a) If the average for the whole protein is above 1.0 then        all residues having average propensity above 1.0 are potentially        antigenic.    -   3. (b) If the average for the whole protein is below 1.0 then        all residues having above the average for the whole protein are        potentially antigenic.    -   4. Find 8-mers where all residues are selected by step 3 above        (6-mers in the original paper)

The Kolaskar and Tongaonkar method is also available from the GCGpackage, and it runs using the command egcg.

Crystal structures also allow identification of residues at whichmutation is likely to alter the activity of the protein. Such residuesinclude, for example, residues that interact with substrate, conservedactive site residues, and residues that are in a region of orderedsecondary structure of involved in tertiary interactions. The mutationsthat are likely to affect activity will vary for different molecularcontexts. Mutations in an active site that will affect activity aretypically substitutions or deletions that eliminate a charge-charge orhydrogen bonding interaction, or introduce a steric interference.Mutations in secondary structure regions or molecular interactionregions that are likely to affect activity include, for example,substitutions that alter the hydrophobicity/hydrophilicity of a region,or that introduce a sufficient strain in a region near or including theactive site so that critical residue(s) in the active site aredisplaced. Such substitutions and/or deletions and/or insertions arerecognized, and the predicted structural and/or energetic effects ofmutations can be calculated using conventional software.

XI. Kinase Activity Assays

A number of different assays for kinase activity can be utilized forassaying for active modulators and/or determining specificity of amodulator for a particular kinase or group or kinases. In addition tothe assay mentioned in the Examples below, one of ordinary skill in theart will know of other assays that can be utilized and can modify anassay for a particular application. For example, numerous papersconcerning kinases described assays that can be used.

An assay for kinase activity that can be used for c-Kit, can beperformed according to the following procedure using purified c-Kitusing the procedure described in the Examples.

Additional alternative assays can employ binding determinations. Forexample, this sort of assay can be formatted either in a fluorescenceresonance energy transfer (FRET) format, or using an AlphaScreen(amplified luminescent proximity homogeneous assay) format by varyingthe donor and acceptor reagents that are attached to streptavidin or thephosphor-specific antibody.

XII. Organic Synthetic Techniques

The versatility of computer-based modulator design and identificationlies in the diversity of structures screened by the computer programs.The computer programs can search databases that contain very largenumbers of molecules and can modify modulators already complexed withthe enzyme with a wide variety of chemical functional groups. Aconsequence of this chemical diversity is that a potential modulator ofkinase function may take a chemical form that is not predictable. A widearray of organic synthetic techniques exist in the art to meet thechallenge of constructing these potential modulators. Many of theseorganic synthetic methods are described in detail in standard referencesources utilized by those skilled in the art. One example of suh areference is March, 1994, Advanced Organic Chemistry; Reactions,Mechanisms and Structure, New York, McGraw Hill. Thus, the techniquesuseful to synthesize a potential modulator of kinase function identifiedby computer-based methods are readily available to those skilled in theart of organic chemical synthesis.

XIII. Administration

The methods and compounds will typically be used in therapy for humanpatients. However, they may also be used to treat similar or identicaldiseases in other vertebrates such as other primates, sports animals,and pets such as horses, dogs and cats.

Suitable dosage forms, in part, depend upon the use or the route ofadministration, for example, oral, transdermal, transmucosal, inhalant,or by injection (parenteral). Such dosage forms should allow thecompound to reach target cells. Other factors are well known in the art,and include considerations such as toxicity and dosage forms that retardthe compound or composition from exerting its effects. Techniques andformulations generally may be found in Remington's PharmaceuticalSciences, 18^(th) ed., Mack Publishing Co., Easton, Pa., 1990 (herebyincorporated by reference herein).

Compounds can be formulated as prodrugs. The term “prodrug,” as usedherein, refers to a compound which, when metabolised, yields the desiredactive compound. Typically, the prodrug is inactive, or less active thanthe active compound, but may provide advantageous handling,administration, or metabolic properties. For example, some prodrugs areesters of the active compound; during metabolysis, the ester group iscleaved to yield the active drug. Also, some prodrugs are activatedenzymatically to yield the active compound, or a compound which, uponfurther chemical reaction, yields the active compound.

Compounds can be formulated as pharmaceutically acceptable salts.Pharmaceutically acceptable salts are non-toxic salts in the amounts andconcentrations at which they are administered. The preparation of suchsalts can facilitate the pharmacological use by altering the physicalcharacteristics of a compound without preventing it from exerting itsphysiological effect. Useful alterations in physical properties includelowering the melting point to facilitate transmucosal administration andincreasing the solubility to facilitate administering higherconcentrations of the drug.

Pharmaceutically acceptable salts include acid addition salts such asthose containing sulfate, chloride, hydrochloride, fumarate, maleate,phosphate, sulfamate, acetate, citrate, lactate, tartrate,methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate,cyclohexylsulfamate and quinate. Pharmaceutically acceptable salts canbe obtained from acids such as hydrochloric acid, maleic acid, sulfuricacid, phosphoric acid, sulfamic acid, acetic acid, citric acid, lacticacid, tartaric acid, malonic acid, methanesulfonic acid, ethanesulfonicacid, benzenesulfonic acid, p-toluenesulfonic acid, cyclohexylsulfamicacid, fumaric acid, and quinic acid.

Pharmaceutically acceptable salts also include basic addition salts suchas those containing benzathine, chloroprocaine, choline, diethanolamine,ethylenediamine, meglumine, procaine, aluminum, calcium, lithium,magnesium, potassium, sodium, ammonium, alkylamine, and zinc, whenacidic functional groups, such as carboxylic acid or phenol are present.For example, see Remington's Pharmaceutical Sciences, 19^(th) ed., MackPublishing Co., Easton, Pa., Vol. 2, p. 1457, 1995. Such salts can beprepared using the appropriate corresponding bases.

Pharmaceutically acceptable salts can be prepared by standardtechniques. For example, the free-base form of a compound is dissolvedin a suitable solvent, such as an aqueous or aqueous-alcohol in solutioncontaining the appropriate acid and then isolated by evaporating thesolution. In another example, a salt is prepared by reacting the freebase and acid in an organic solvent.

The pharmaceutically acceptable salt of the different compounds may bepresent as a complex. Examples of complexes include 8-chlorotheophyllinecomplex (analogous to, e.g., dimenhydrinate: diphenhydramine8-chlorotheophylline (1:1) complex; Dramamine) and various cyclodextrininclusion complexes.

Carriers or excipients can be used to produce pharmaceuticalcompositions. The carriers or excipients can be chosen to facilitateadministration of the compound. Examples of carriers include calciumcarbonate, calcium phosphate, various sugars such as lactose, glucose,or sucrose, or types of starch, cellulose derivatives, gelatin,vegetable oils, polyethylene glycols and physiologically compatiblesolvents. Examples of physiologically compatible solvents includesterile solutions of water for injection (WFI), saline solution, anddextrose.

The compounds can be administered by different routes includingintravenous, intraperitoneal, subcutaneous, intramuscular, oral,transmucosal, rectal, inhalant or transdermal. Oral administration ispreferred. For oral administration, for example, the compounds can beformulated into conventional oral dosage forms such as capsules,tablets, and liquid preparations such as syrups, elixirs, andconcentrated drops.

Pharmaceutical preparations for oral use can be obtained, for example,by combining the active compounds with solid excipients, optionallygrinding a resulting mixture, and processing the mixture of granules,after adding suitable auxiliaries, if desired, to obtain tablets ordragee cores. Suitable excipients are, in particular, fillers such assugars, including lactose, sucrose, mannitol, or sorbitol; cellulosepreparations, for example, maize starch, wheat starch, rice starch,potato starch, gelatin, gum tragacanth, methyl cellulose,hydroxypropylmethyl-cellulose, sodium carboxymethylcellulose (CMC),and/or polyvinylpyrrolidone (PVP: povidone). If desired, disintegratingagents may be added, such as the cross-linked polyvinylpyrrolidone,agar, or alginic acid, or a salt thereof such as sodium alginate.

Dragee cores are provided with suitable coatings. For this purpose,concentrated sugar solutions may be used, which may optionally contain,for example, gum arabic, talc, poly-vinylpyrrolidone, carbopol gel,polyethylene glycol (PEG), and/or titanium dioxide, lacquer solutions,and suitable organic solvents or solvent mixtures. Dye-stuffs orpigments may be added to the tablets or dragee coatings foridentification or to characterize different combinations of activecompound doses.

Pharmaceutical preparations that can be used orally include push-fitcapsules made of gelatin (“gelcaps”), as well as soft, sealed capsulesmade of gelatin, and a plasticizer, such as glycerol or sorbitol. Thepush-fit capsules can contain the active ingredients in admixture withfiller such as lactose, binders such as starches, and/or lubricants suchas talc or magnesium stearate and, optionally, stabilizers. In softcapsules, the active compounds may be dissolved or suspended in suitableliquids, such as fatty oils, liquid paraffin, or liquid polyethyleneglycols (PEGs). In addition, stabilizers may be added.

Alternatively, injection (parenteral administration) may be used, e.g.,intramuscular, intravenous, intraperitoneal, and/or subcutaneous. Forinjection, the compounds of the invention are formulated in sterileliquid solutions, preferably in physiologically compatible buffers orsolutions, such as saline solution, Hank's solution, or Ringer'ssolution. In addition, the compounds may be formulated in solid form andredissolved or suspended immediately prior to use. Lyophilized forms canalso be produced.

Administration can also be by transmucosal, inhalant, or transdermalmeans. For transmucosal or transdermal administration, penetrantsappropriate to the barrier to be permeated are used in the formulation.Such penetrants are generally known in the art, and include, forexample, for transmucosal administration, bile salts and fusidic acidderivatives. In addition, detergents may be used to facilitatepermeation. Transmucosal administration, for example, may be throughnasal sprays or suppositories (rectal or vaginal).

For inhalants, compounds of the invention may be formulated as drypowder or a suitable solution, suspension, or aerosol. Powders andsolutions may be formulated with suitable additives known in the art.For example, powders may include a suitable powder base such as lacatoseor starch, and solutions may comprise propylene glycol, sterile water,ethanol, sodium chloride and other additives, such as acid, alkali andbuffer salts. Such solutions or suspensions may be administered byinhaling via spray, pump, atomizer, or nebulizer and the like. Thecompounds of the invention may also be used in combination with otherinhaled therapies, for example corticosteroids such as fluticasoneproprionate, beclomethasone dipropionate, triamcinolone acetonide,budesonide, and mometasone furoate; beta agonists such as albuterol,salmeterol, and formoterol; anticholinergic agents such as ipratropriumbromide or tiotropium; vasodilators such as treprostinal and iloprost;enzymes such as DNAase; therapeutic proteins; immunoglobulin antibodies;an oligonucleotide, such as single or double stranded DNA or RNA, siRNA;antibiotics such as tobramycin; muscarinic receptor antagonists;leukotriene antagonists; cytokine antagonists; protease inhibitors;cromolyn sodium; nedocril sodium; and sodium cromoglycate.

It is understood that use in combination includes delivery of compoundsof the invention and one or more other inhaled therapeutics together inany formulation, including formulations where the two compounds arechemically linked such that they maintain their therapeutic activitywhen administered. Combination use includes administration ofco-formulations or formulations of chemically joined compounds, orco-administration of the compounds in separate formulations. Separateformulations may be co-administered by delivery from the same inhalantdevice, or can be co-administered from separate inhalant devices, whereco-administration in this case means administered within a short time ofeach other. Co-formulations of a compound of the invention and one ormore additional inhaled therapies includes preparation of the materialstogether such that they can be administered by one inhalant device,including the separate compounds combined in one formulation, orcompounds that are modified such that they are chemically joined, yetstill maintain their biological activity.

The amounts of various compound to be administered can be determined bystandard procedures taking into account factors such as the compoundIC₅₀, the biological half-life of the compound, the age, size, andweight of the patient, and the disorder associated with the patient. Theimportance of these and other factors are well known to those ofordinary skill in the art. Generally, a dose will be between about 0.01and 50 mg/kg, preferably 0.1 and 20 mg/kg of the patient being treated.Multiple doses may be used.

XIV. Manipulation of c-Kit

As the full-length coding sequence and amino acid sequence of c-Kit fromvarious mammals including human is known, cloning, construction ofrecombinant c-Kit, production and purification of recombinant protein,introduction of c-Kit into other organisms, and other molecularbiological manipulations of c-Kit are readily performed.

Techniques for the manipulation of nucleic acids, such as, e.g.,subcloning, labeling probes (e.g., random-primer labeling using Klenowpolymerase, nick translation, amplification), sequencing, hybridizationand the like are well disclosed in the scientific and patent literature,see, e.g., Sambrook, ed., Molecular Cloning: a Laboratory Manual (2nded.), Vols. 1-3, Cold Spring Harbor Laboratory, (1989); CurrentProtocols in Molecular Biology, Ausubel, ed. John Wiley & Sons, Inc.,New York (1997); Laboratory Techniques in Biochemistry and MolecularBiology: Hybridization With Nucleic Acid Probes, Part I. Theory andNucleic Acid Preparation, Tijssen, ed. Elsevier, N.Y. (1993).

Nucleic acid sequences can be amplified as necessary for further useusing amplification methods, such as PCR, isothermal methods, rollingcircle methods, etc., are well known to the skilled artisan. See, e.g.,Saiki, “Amplification of Genomic DNA” in PCR Protocols, Innis et al.,Eds., Academic Press, San Diego, Calif. 1990, pp 13-20; Wharam et al.,Nucleic Acids Res. 2001 29:E54-E54; Hafner et al., Biotechniques 200130:852-6, 858, 860; Zhong et al., Biotechniques 2001 30:852-6, 858,860).

Nucleic acids, vectors, capsids, polypeptides, and the like can beanalyzed and quantified by any of a number of general means well knownto those of skill in the art. These include, e.g., analyticalbiochemical methods such as NMR, spectrophotometry, radiography,electrophoresis, capillary electrophoresis, high performance liquidchromatography (HPLC), thin layer chromatography (TLC), andhyperdiffusion chromatography, various immunological methods, e.g. fluidor gel precipitin reactions, immunodiffusion, immuno-electrophoresis,radioimmunoassays (RIAs), enzyme-linked immunosorbent assays (ELISAs),immuno-fluorescent assays, Southern analysis, Northern analysis,dot-blot analysis, gel electrophoresis (e.g., SDS-PAGE), nucleic acid ortarget or signal amplification methods, radiolabeling, scintillationcounting, and affinity chromatography.

Obtaining and manipulating nucleic acids used to practice the methods ofthe invention can be performed by cloning from genomic samples, and, ifdesired, screening and re-cloning inserts isolated or amplified from,e.g., genomic clones or cDNA clones. Sources of nucleic acid used in themethods of the invention include genomic or cDNA libraries contained in,e.g., mammalian artificial chromosomes (MACs), see, e.g., U.S. Pat. Nos.5,721,118; 6,025,155; human artificial chromosomes, see, e.g., Rosenfeld(1997) Nat. Genet. 15:333-335; yeast artificial chromosomes (YAC);bacterial artificial chromosomes (BAC); P1 artificial chromosomes, see,e.g., Woon (1998) Genomics 50:306-316; P1-derived vectors (PACs), see,e.g., Kern (1997) Biotechniques 23:120-124; cosmids, recombinantviruses, phages or plasmids.

The nucleic acids of the invention can be operatively linked to apromoter. A promoter can be one motif or an array of nucleic acidcontrol sequences which direct transcription of a nucleic acid. Apromoter can include necessary nucleic acid sequences near the startsite of transcription, such as, in the case of a polymerase II typepromoter, a TATA element. A promoter also optionally includes distalenhancer or repressor elements which can be located as much as severalthousand base pairs from the start site of transcription. A“constitutive” promoter is a promoter which is active under mostenvironmental and developmental conditions. An “inducible” promoter is apromoter which is under environmental or developmental regulation. A“tissue specific” promoter is active in certain tissue types of anorganism, but not in other tissue types from the same organism. The term“operably linked” refers to a functional linkage between a nucleic acidexpression control sequence (such as a promoter, or array oftranscription factor binding sites) and a second nucleic acid sequence,wherein the expression control sequence directs transcription of thenucleic acid corresponding to the second sequence.

The nucleic acids of the invention can also be provided in expressionvectors and cloning vehicles, e.g., sequences encoding the polypeptidesof the invention. Expression vectors and cloning vehicles of theinvention can comprise viral particles, baculovirus, phage, plasmids,phagemids, cosmids, fosmids, bacterial artificial chromosomes, viral DNA(e.g., vaccinia, adenovirus, foul pox virus, pseudorabies andderivatives of SV40), P1-based artificial chromosomes, yeast plasmids,yeast artificial chromosomes, and any other vectors specific forspecific hosts of interest (such as bacillus, Aspergillus and yeast).Vectors of the invention can include chromosomal, non-chromosomal andsynthetic DNA sequences. Large numbers of suitable vectors are known tothose of skill in the art, and are commercially available.

The nucleic acids of the invention can be cloned, if desired, into anyof a variety of vectors using routine molecular biological methods;methods for cloning in vitro amplified nucleic acids are disclosed,e.g., U.S. Pat. No. 5,426,039. To facilitate cloning of amplifiedsequences, restriction enzyme sites can be “built into” a PCR primerpair. Vectors may be introduced into a genome or into the cytoplasm or anucleus of a cell and expressed by a variety of conventional techniques,well described in the scientific and patent literature. See, e.g.,Roberts (1987) Nature 328:731; Schneider (1995) Protein Expr. Purif6435:10; Sambrook, Tijssen or Ausubel. The vectors can be isolated fromnatural sources, obtained from such sources as ATCC or GenBanklibraries, or prepared by synthetic or recombinant methods. For example,the nucleic acids of the invention can be expressed in expressioncassettes, vectors or viruses which are stably or transiently expressedin cells (e.g., episomal expression systems). Selection markers can beincorporated into expression cassettes and vectors to confer aselectable phenotype on transformed cells and sequences. For example,selection markers can code for episomal maintenance and replication suchthat integration into the host genome is not required.

In one aspect, the nucleic acids of the invention are administered invivo for in situ expression of the peptides or polypeptides of theinvention. The nucleic acids can be administered as “naked DNA” (see,e.g., U.S. Pat. No. 5,580,859) or in the form of an expression vector,e.g., a recombinant virus. The nucleic acids can be administered by anyroute, including peri- or intra-tumorally, as described below. Vectorsadministered in vivo can be derived from viral genomes, includingrecombinantly modified enveloped or non-enveloped DNA and RNA viruses,preferably selected from baculoviridiae, parvoviridiae, picornoviridiae,herpesveridiae, poxyiridae, adenoviridiae, or picornnaviridiae. Chimericvectors may also be employed which exploit advantageous merits of eachof the parent vector properties (See e.g., Feng (1997) NatureBiotechnology 15:866-870). Such viral genomes may be modified byrecombinant DNA techniques to include the nucleic acids of theinvention; and may be further engineered to be replication deficient,conditionally replicating or replication competent. In alternativeaspects, vectors are derived from the adenoviral (e.g., replicationincompetent vectors derived from the human adenovirus genome, see, e.g.,U.S. Pat. Nos. 6,096,718; 6,110,458; 6,113,913; 5,631,236);adeno-associated viral and retroviral genomes. Retroviral vectors caninclude those based upon murine leukemia virus (MuLV), gibbon apeleukemia virus (GaLV), Simian Immuno deficiency virus (SIV), humanimmuno deficiency virus (HIV), and combinations thereof; see, e.g., U.S.Pat. Nos. 6,117,681; 6,107,478; 5,658,775; 5,449,614; Buchscher (1992)J. Virol. 66:2731-2739; Johann (1992) J. Virol. 66:1635-1640).Adeno-associated virus (AAV)-based vectors can be used to transducecells with target nucleic acids, e.g., in the in vitro production ofnucleic acids and peptides, and in in vivo and ex vivo gene therapyprocedures; see, e.g., U.S. Pat. Nos. 6,110,456; 5,474,935; Okada (1996)Gene Ther. 3:957-964.

The present invention also relates to fusion proteins, and nucleic acidsencoding them. A polypeptide of the invention can be fused to aheterologous peptide or polypeptide, such as N-terminal identificationpeptides which impart desired characteristics, such as increasedstability or simplified purification. Peptides and polypeptides of theinvention can also be synthesized and expressed as fusion proteins withone or more additional domains linked thereto for, e.g., producing amore immunogenic peptide, to more readily isolate a recombinantlysynthesized peptide, to identify and isolate antibodies andantibody-expressing B cells, and the like. Detection and purificationfacilitating domains include, e.g., metal chelating peptides such aspolyhistidine tracts and histidine-tryptophan modules that allowpurification on immobilized metals, protein A domains that allowpurification on immobilized immunoglobulin, and the domain utilized inthe FLAGS extension/affinity purification system (Immunex Corp, SeattleWash.). The inclusion of a cleavable linker sequences such as Factor Xaor enterokinase (Invitrogen, San Diego Calif.) between a purificationdomain and the motif-comprising peptide or polypeptide to facilitatepurification. For example, an expression vector can include anepitope-encoding nucleic acid sequence linked to six histidine residuesfollowed by a thioredoxin and an enterokinase cleavage site (see e.g.,Williams (1995) Biochemistry 34:1787-1797; Dobeli (1998) Protein Expr.Purif 12:404-414). The histidine residues facilitate detection andpurification while the enterokinase cleavage site provides a means forpurifying the epitope from the remainder of the fusion protein. In oneaspect, a nucleic acid encoding a polypeptide of the invention isassembled in appropriate phase with a leader sequence capable ofdirecting secretion of the translated polypeptide or fragment thereof.Technology pertaining to vectors encoding fusion proteins andapplication of fusion proteins are well disclosed in the scientific andpatent literature, see e.g., Kroll (1993) DNA Cell. Biol. 12:441-53.

The nucleic acids and polypeptides of the invention can be bound to asolid support, e.g., for use in screening and diagnostic methods. Solidsupports can include, e.g., membranes (e.g., nitrocellulose or nylon), amicrotiter dish (e.g., PVC, polypropylene, or polystyrene), a test tube(glass or plastic), a dip stick (e.g., glass, PVC, polypropylene,polystyrene, latex and the like), a microfuge tube, or a glass, silica,plastic, metallic or polymer bead or other substrate such as paper. Onesolid support uses a metal (e.g., cobalt or nickel)-comprising columnwhich binds with specificity to a histidine tag engineered onto apeptide.

Adhesion of molecules to a solid support can be direct (i.e., themolecule contacts the solid support) or indirect (a “linker” is bound tothe support and the molecule of interest binds to this linker).Molecules can be immobilized either covalently (e.g., utilizing singlereactive thiol groups of cysteine residues (see, e.g., Colliuod (1993)Bioconjugate Chem. 4:528-536) or non-covalently but specifically (e.g.,via immobilized antibodies (see, e.g., Schuhmann (1991) Adv. Mater.3:388-391; Lu (1995) Anal. Chem. 67:83-87; the biotin/strepavidin system(see, e.g., Iwane (1997) Biophys. Biochem. Res. Comm. 230:76-80); metalchelating, e.g., Langmuir-Blodgett films (see, e.g., Ng (1995) Langmuir11:4048-55); metal-chelating self-assembled monolayers (see, e.g., Sigal(1996) Anal. Chem. 68:490-497) for binding of polyhistidine fusions.

Indirect binding can be achieved using a variety of linkers which arecommercially available. The reactive ends can be any of a variety offunctionalities including, but not limited to: amino reacting ends suchas N-hydroxysuccinimide (NHS) active esters, imidoesters, aldehydes,epoxides, sulfonyl halides, isocyanate, isothiocyanate, and nitroarylhalides; and thiol reacting ends such as pyridyl disulfides, maleimides,thiophthalimides, and active halogens. The heterobifunctionalcrosslinking reagents have two different reactive ends, e.g., anamino-reactive end and a thiol-reactive end, while homobifunctionalreagents have two similar reactive ends, e.g., bismaleimidohexane (BMH)which permits the cross-linking of sulfhydryl-containing compounds. Thespacer can be of varying length and be aliphatic or aromatic. Examplesof commercially available homobifunctional cross-linking reagentsinclude, but are not limited to, the imidoesters such as dimethyladipimidate dihydrochloride (DMA); dimethyl pimelimidate dihydrochloride(DMP); and dimethyl suberimidate dihydrochloride (DMS).Heterobifunctional reagents include commercially available activehalogen-NHS active esters coupling agents such as N-succinimidylbromoacetate and N-succinimidyl (4-iodoacetyl)aminobenzoate (SIAB) andthe sulfosuccinimidyl derivatives such assulfosuccinimidyl(4-iodoacetyl)aminobenzoate (sulfo-SIAB) (Pierce).Another group of coupling agents is the heterobifunctional and thiolcleavable agents such as N-succinimidyl 3-(2-pyridyldithio)propionate(SPDP) (Pierce Chemicals, Rockford, Ill.).

Antibodies can also be used for binding polypeptides and peptides of theinvention to a solid support. This can be done directly by bindingpeptide-specific antibodies to the column or it can be done by creatingfusion protein chimeras comprising motif-containing peptides linked to,e.g., a known epitope (e.g., a tag (e.g., FLAG, myc) or an appropriateimmunoglobulin constant domain sequence (an “immunoadhesin,” see, e.g.,Capon (1989) Nature 377:525-531 (1989).

Nucleic acids or polypeptides of the invention can be immobilized to orapplied to an array. Arrays can be used to screen for or monitorlibraries of compositions (e.g., small molecules, antibodies, nucleicacids, etc.) for their ability to bind to or modulate the activity of anucleic acid or a polypeptide of the invention. For example, in oneaspect of the invention, a monitored parameter is transcript expressionof a gene comprising a nucleic acid of the invention. One or more, or,all the transcripts of a cell can be measured by hybridization of asample comprising transcripts of the cell, or, nucleic acidsrepresentative of or complementary to transcripts of a cell, byhybridization to immobilized nucleic acids on an array, or “biochip.” Byusing an “array” of nucleic acids on a microchip, some or all of thetranscripts of a cell can be simultaneously quantified. Alternatively,arrays comprising genomic nucleic acid can also be used to determine thegenotype of a newly engineered strain made by the methods of theinvention. Polypeptide arrays” can also be used to simultaneouslyquantify a plurality of proteins.

The terms “array” or “microarray” or “biochip” or “chip” as used hereinis a plurality of target elements, each target element comprising adefined amount of one or more polypeptides (including antibodies) ornucleic acids immobilized onto a defined area of a substrate surface. Inpracticing the methods of the invention, any known array and/or methodof making and using arrays can be incorporated in whole or in part, orvariations thereof, as disclosed, for example, in U.S. Pat. Nos.6,277,628; 6,277,489; 6,261,776; 6,258,606; 6,054,270; 6,048,695;6,045,996; 6,022,963; 6,013,440; 5,965,452; 5,959,098; 5,856,174;5,830,645; 5,770,456; 5,632,957; 5,556,752; 5,143,854; 5,807,522;5,800,992; 5,744,305; 5,700,637; 5,556,752; 5,434,049; see also, e.g.,WO 99/51773; WO 99/09217; WO 97/46313; WO 96/17958; see also, e.g.,Johnston (1998) Curr. Biol. 8:R171-R174; Schummer (1997) Biotechniques23:1087-1092; Kem (1997) Biotechniques 23:120-124; Solinas-Toldo (1997)Genes, Chromosomes & Cancer 20:399-407; Bowtell (1999) Nature GeneticsSupp. 21:25-32. See also published U.S. patent applications Nos.20010018642; 20010019827; 20010016322; 20010014449; 20010014448;20010012537; 20010008765.

Host Cells and Transformed Cells

The invention also provides a transformed cell comprising a nucleic acidsequence of the invention, e.g., a sequence encoding a polypeptide ofthe invention, or a vector of the invention. The host cell may be any ofthe host cells familiar to those skilled in the art, includingprokaryotic cells, eukaryotic cells, such as bacterial cells, fungalcells, yeast cells, mammalian cells, insect cells, or plant cells.Exemplary bacterial cells include E. coli, Streptomyces, Bacillussubtilis, Salmonella typhimurium and various species within the generaPseudomonas, Streptomyces, and Staphylococcus. Exemplary insect cellsinclude Drosophila S2 and Spodoptera Sf9. Exemplary animal cells includeCHO, COS or Bowes melanoma or any mouse or human cell line. Theselection of an appropriate host is within the abilities of thoseskilled in the art.

Vectors may be introduced into the host cells using any of a variety oftechniques, including transformation, transfection, transduction, viralinfection, gene guns, or Ti-mediated gene transfer. Particular methodsinclude calcium phosphate transfection, DEAE-Dextran mediatedtransfection, lipofection, or electroporation.

Engineered host cells can be cultured in conventional nutrient mediamodified as appropriate for activating promoters, selectingtransformants or amplifying the genes of the invention. Followingtransformation of a suitable host strain and growth of the host strainto an appropriate cell density, the selected promoter may be induced byappropriate means (e.g., temperature shift or chemical induction) andthe cells may be cultured for an additional period to allow them toproduce the desired polypeptide or fragment thereof.

Cells can be harvested by centrifugation, disrupted by physical orchemical means, and the resulting crude extract is retained for furtherpurification. Microbial cells employed for expression of proteins can bedisrupted by any convenient method, including freeze-thaw cycling,sonication, mechanical disruption, or use of cell lysing agents. Suchmethods are well known to those skilled in the art. The expressedpolypeptide or fragment can be recovered and purified from recombinantcell cultures by methods including ammonium sulfate or ethanolprecipitation, acid extraction, anion or cation exchange chromatography,phosphocellulose chromatography, hydrophobic interaction chromatography,affinity chromatography, hydroxylapatite chromatography and lectinchromatography. Protein refolding steps can be used, as necessary, incompleting configuration of the polypeptide. If desired, highperformance liquid chromatography (HPLC) can be employed for finalpurification steps.

Various mammalian cell culture systems can also be employed to expressrecombinant protein. Examples of mammalian expression systems includethe COS-7 lines of monkey kidney fibroblasts and other cell linescapable of expressing proteins from a compatible vector, such as theC127, 3T3, CHO, HeLa and BHK cell lines.

The constructs in host cells can be used in a conventional manner toproduce the gene product encoded by the recombinant sequence. Dependingupon the host employed in a recombinant production procedure, thepolypeptides produced by host cells containing the vector may beglycosylated or may be non-glycosylated. Polypeptides of the inventionmay or may not also include an initial methionine amino acid residue.

Cell-free translation systems can also be employed to produce apolypeptide of the invention. Cell-free translation systems can usemRNAs transcribed from a DNA construct comprising a promoter operablylinked to a nucleic acid encoding the polypeptide or fragment thereof.In some aspects, the DNA construct may be linearized prior to conductingan in vitro transcription reaction. The transcribed mRNA is thenincubated with an appropriate cell-free translation extract, such as arabbit reticulocyte extract, to produce the desired polypeptide orfragment thereof.

The expression vectors can contain one or more selectable marker genesto provide a phenotypic trait for selection of transformed host cellssuch as dihydrofolate reductase or neomycin resistance for eukaryoticcell culture, or such as tetracycline or ampicillin resistance in E.coli.

For transient expression in mammalian cells, cDNA encoding a polypeptideof interest may be incorporated into a mammalian expression vector, e.g.pcDNA1, which is available commercially from Invitrogen Corporation (SanDiego, Calif., U.S.A.; catalogue number V490-20). This is amultifunctional 4.2 kb plasmid vector designed for cDNA expression ineukaryotic systems, and cDNA analysis in prokaryotes, incorporated onthe vector are the CMV promoter and enhancer, splice segment andpolyadenylation signal, an SV40 and Polyoma virus origin of replication,and M13 origin to rescue single strand DNA for sequencing andmutagenesis, Sp6 and T7 RNA promoters for the production of sense andanti-sense RNA transcripts and a Col E1-like high copy plasmid origin. Apolylinker is located appropriately downstream of the CMV promoter (and3′ of the T7 promoter).

The cDNA insert may be first released from the above phagemidincorporated at appropriate restriction sites in the pcDNAI polylinker.Sequencing across the junctions may be performed to confirm properinsert orientation in pcDNAI. The resulting plasmid may then beintroduced for transient expression into a selected mammalian cell host,for example, the monkey-derived, fibroblast like cells of the COS-1lineage (available from the American Type Culture Collection, Rockville,Md. as ATCC CRL 1650).

For transient expression of the protein-encoding DNA, for example, COS-1cells may be transfected with approximately 8 μg DNA per 106 COS cells,by DEAE-mediated DNA transfection and treated with chloroquine accordingto the procedures described by Sambrook et al, Molecular Cloning: ALaboratory Manual, 1989, Cold Spring Harbor Laboratory Press, ColdSpring Harbor N.Y., pp. 16.30-16.37. An exemplary method is as follows.Briefly, COS-1 cells are plated at a density of 5×10⁶ cells/dish andthen grown for 24 hours in FBS-supplemented DMEM/F12 medium. Medium isthen removed and cells are washed in PBS and then in medium. Atransfection solution containing DEAE dextran (0.4 mg/ml), 100 μMchloroquine, 10% NuSerum, DNA (0.4 mg/ml) in DMEM/F12 medium is thenapplied on the cells 10 ml volume. After incubation for 3 hours at 37°C., cells are washed in PBS and medium as just described and thenshocked for 1 minute with 10% DMSO in DMEM/F12 medium. Cells are allowedto grow for 2-3 days in 10% FBS-supplemented medium, and at the end ofincubation dishes are placed on ice, washed with ice cold PBS and thenremoved by scraping. Cells are then harvested by centrifugation at 1000rpm for 10 minutes and the cellular pellet is frozen in liquid nitrogen,for subsequent use in protein expression. Northern blot analysis of athawed aliquot of frozen cells may be used to confirm expression ofreceptor-encoding cDNA in cells under storage.

In a like manner, stably transfected cell lines can also prepared, forexample, using two different cell types as host: CHO K1 and CHO Pro5. Toconstruct these cell lines, cDNA coding for the relevant protein may beincorporated into the mammalian expression vector pRC/CMV (Invitrogen),which enables stable expression. Insertion at this site places the cDNAunder the expression control of the cytomegalovirus promoter andupstream of the polyadenylation site and terminator of the bovine growthhormone gene, and into a vector background comprising the neomycinresistance gene (driven by the SV40 early promoter) as selectablemarker.

An exemplary protocol to introduce plasmids constructed as describedabove is as follows. The host CHO cells are first seeded at a density of5×10⁵ in 10% FBS-supplemented MEM medium. After growth for 24 hours,fresh medium is added to the plates and three hours later, the cells aretransfected using the calcium phosphate-DNA co-precipitation procedure(Sambrook et al, supra). Briefly, 3 μg of DNA is mixed and incubatedwith buffered calcium solution for 10 minutes at room temperature. Anequal volume of buffered phosphate solution is added and the suspensionis incubated for 15 minutes at room temperature. Next, the incubatedsuspension is applied to the cells for 4 hours, removed and cells wereshocked with medium containing 15% glycerol. Three minutes later, cellsare washed with medium and incubated for 24 hours at normal growthconditions. Cells resistant to neomycin are selected in 10%FBS-supplemented alpha-MEM medium containing G418 (1 mg/ml). Individualcolonies of G418-resistant cells are isolated about 2-3 weeks later,clonally selected and then propagated for assay purposes.

EXAMPLES

A number of examples involved in the present invention are describedbelow. In most cases, alternative techniques could also be used. Theexamples are intended to be illustrative and are not limiting orrestrictive to the scope of the invention.

Example 1 Synthesis of Compound of Formula Ia, where R¹, R³, R⁴, and R⁵are Hydrogen

Step-1—Synthesis of Compound 2.

Compound 2 was synthesized from commercially available 7-azaindolefollowing the literature procedure (Robinson, J. Am. Chem. Soc., 1955,77, p. 457).

Step-2—Synthesis of compound of formula II.

Compound of formula II was synthesized by deprotonation using base (e.g.BuLi, NaH) in aprotic solvent like THF or ether and reacting the anionwith a silyl chloride (e.g. TIPS) or an anhydride (e.g. Boc anhydride).The product was isolated by following standard procedure (quenching withice-cold brine, work up, and purification by flash silica gelchromatography).

Step-3—Synthesis of Compound of Formula Ia.

Compounds of Formula Ia was synthesized through the reaction ofcompounds of formula II with isopropyl chloroformate (or ethylchloroformate) at room temperature in toluene to give a 3-chloromethylintermediate. This intermediate cooled to −78° C. and was immediatelyreacted with an organocopper reagent, which was generated from thereaction between a Grignard reagent (or organolithium reagent) and asolution of copper cyanide and LiCl. The mixture was stirred at −78° C.for one hour then allowed to warm to room temperature. The reaction wasquenched with a solution of 4:1 ammonium chloride: ammonium Hydroxide.The reaction was worked up in the usual manner and purified by flashsilica gel chromatography to give the nitrogen-protected product. Thefinal product can be realized through the deprotection of the protectinggroup (Boc, TIPS) using standard conditions (TFA or NH₄F) at roomtemperature.

Step-1—Synthesis of Compound 3

Compound 3 was synthesized by reacting commercially available7-azaindole, compound 1, with hexamethyltetramine and acetic acid inwater with heating to reflux for two hours. After cooling, the desiredproduct precipitated and was collected by filtration.

Step-2—Synthesis of Compound of Formula III

Compound of formula III, where P is a protecting group, was synthesizedby reacting compound 3 with an appropriate reagent to introduce aprotecting group (e.g. tert-butyloxycarbonyl di anhydride) and a base(e.g. sodium hydride) in a solvent (e.g. THF) typically at roomtemperature for 12-18 hours. The product can be isolated by conventionalmeans (e.g. extraction).

Step-3—Synthesis of Compound of Formula IV

Compound of formula IV was synthesized by reacting compound of formulaIII in a solvent (e.g. 1,2-dimethoxyethane) with a Grignard reagent ofthe formula R²⁴MgCl (e.g. phenyl magnesium bromide) or an equivalentnucleophile in a solvent (e.g. THF) under inert atmosphere cooledtypically to −10° C. The reaction was typically allowed to warm to roomtemperature and stirred for 12-18 hours. The desired product waspurified by reverse phase high pressure liquid chromatography.

Step-4—Synthesis of an Intermediate of Compound of Formula Ia where R²is Aralkyl or Heteroaralkyl and R²⁴ is Aryl or Heteroaryl

An intermediate of compound of Formula Ia was synthesized by reactingcompound of Formula IV with a reducing agent (e.g. sodium borohydride)in a solvent (e.g. ethanol) typically with heating to 80° C. for 1-4hours. The reaction was quenched with the addition of methanol andconcentrated and purified by reverse phase high performance liquidchromatography.

Step-5—Synthesis of Compound of Formula Ia where R² is Aralkyl orHeteroaralkyl and R²⁴ is Aryl or Heteroaryl

Compound of Formula Ia where R² is aralkyl or heteroaralkyl and R²⁴ isaryl or heteroaryl was synthesized by reacting the intermediate fromStep 4 with an appropriate reagent to remove the protecting group, P,(e.g. hydrochloric acid) in an appropriate solvent (e.g. dioxane). Thefinal product was isolated by standard procedures (e.g. reverse phasepreparative high pressure liquid chromatography).

Step-1—Synthesis of Compound of Formula Ib, where R² is Aralkyl orHeteroaralkyl and R²⁴ is Aryl or Heteroaryl

Compound of Formula Ib, where R² is aralkyl or heteroaralkyl and R²⁴ isaryl or heteroaryl, was synthesized by reacting compound 1 with anactivating agent (e.g. methyl magnesium bromide and zinc dichloride oranhydrous aluminum chloride) and an aryl acid chlorides (e.g benzoylchloride) or heteroaryl acid chlorides (nicotinic acid chloride) in aninert solvent (e.g. methylene chloride), under inert atmosphere (e.g.argon), at room temperature or with heating up to reflux for 18-24hours. The product was isolated by standard procedures (e.g. extractionand silica-gel chromatography).

Example 2 Synthesis of Key IntermediateDimethyl-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-amine(6)

Step-1—Synthesis of dimethyl-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-amine(2).

Into a 3-neck round bottom flask was added Isopropyl alcohol (320.0 mL)followed by the addition of 1H-pyrrolo[2,3-b]pyridine 1 (7.10 g, 60.1mmol), dimethylamine hydrochloride (5.4 g, 0.066 mol), and formaldehyde(2.0 g, 0.066 mol). The reaction mixture was stirred at room temperaturefor 12 hours, and then refluxed for 30 minutes. The suspension solutionwas evaporated to dryness in vacuo. To the residue was added water (60.0mL, 3.33 mol) and concentrated hydrochloric acid (6.0 mL, 0.20 mol). Thewater layer was extracted with ether and the aqueous layer wasneutralized with potassium carbonate. The aqueous layer was extractedwith methylene chloride, dried over sodium sulfate and concentrated togive product, which was then further washed with ether and dried toafford the product 2 (7.1 g, yield 67.4%), as a white solid.

Step-2—Synthesis ofdimethyl-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-amine(4).

Into a round bottom flask 7-Azagramine 2 (5.38 g, 30.7 mmol), andN,N-dimethylformamide (25.0 mL), and sodium hydride (1.35 g, 33.8 mol).Into the reaction was added triisopropylsilyl chloride (6.8 mL, 0.032mol). The reaction was stirred at 20 Celsius for 12 hours. The reactionmixture was poured into water, extracted with ethyl acetate. The organiclayer was washed with brine, dried over sodium sulfate, concentrated andpurified with biotage to give product 3 (6.0 g, yield=58.8%) as acolorless oil.

Step-3—Synthesis of3-chloromethyl-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (5).

Into a round bottom flask was added compound 3 (500.0 mg, 1.51 mmol) andtoluene (5.0 mL, 0.047 mol) under an atmosphere of nitrogen. Into thereaction mixture, was added 1.0 M of isopropyl chloroformate in toluene(1.6 mL) slowly at room temperature. The reaction mixture was stirredfor another 2 hours to give desired product 5 using for next stepwithout purification.

Step-4—Synthesis of3-(6-Chloro-pyridin-3-ylmethyl)-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine(6, where X=Cl).

Into a round bottom flask was added 5-iodo-2-chloro-pyridine (315.0 mg,1.32 mmol) or 5-iodo-2-bromo-pyridine and tetrahydrofuran (12.0 mL, 0.15mol) at −40 Celsius under an atmosphere of nitrogen. Into the reactionwas added 2.0 M of isopropylmagnesium chloride in tetrahydrofuran (0.72mL, 1.44 mmol). The reaction mixture was stirred for 40 minutes at 40Celsius. TLC (hexane/ethyl acetate 2:1) indicated no starting material.Into the reaction mixture was added 0.6 M of CuCN.2LiCl intetrahydrofuran (2.4 mL, 1.44 mmol). The reaction mixture was allowed toroom temperature for 5 min and trimethyl phosphite (0.29 mL, 2.4 mmol)was added. After 10 minutes, this solution was added into a round bottomflask, which contains compound 5 (315.0 mg, prepared in situ from thecorresponding gramine 4 (323 mg, 0.98 mmol)) and toluene (8.0 mL). Thereaction was stirred at 20 Celsius for 40 hours. The reaction mixturewas poured into water and the product extracted with ethyl acetate. Theorganic layer was washed with brine, dried over sodium sulfate,concentrated and purified with biotage (methylene chloride/methanol1:10) to give product 6, where X=Cl, (230 mg, yield=59.0%) as a whitesolid. The reaction conditions, work up procedure, and purifications forcompound 6 where X=Br is same as that for the synthesis of compound 6where X=Cl.

Example 3 Synthesis of Key Intermediate(6-Chloro-pyridin-3-yl)-(1H-pyrrolo[2,3-b]pyridin-3-yl)-methanone (7)

Into a round bottom flask was added aluminum trichloride (16.0 g, 0.12mol) and methylene chloride (100.0 mL) under an atmosphere of nitrogen.Into the reaction mixture, was added 1H-Pyrrolo[2,3-b]pyridine 1 (3.2 g,0.027 mol) in methylene dichloride (20.0 mL). The reaction was stirredat room temperature for 70.0 minutes, and then6-Chloropyridine-3-carbonyl chloride 8 (5.4 g, 0.031 mol) in methylenechloride (10.0 mL) was added. The reaction mixture was stirred at roomtemperature for 3 hours. Methanol (10 mL) was added to the reactionmixture and the solvent was evaporated in vacuo. The residue was pouredinto water, and the precipitated product was removed by filtration. Theaqueous layer was extracted with ethyl acetate, and then the organiclayer was dried and concentrated and combined with the solid isolated byfiltration to give 7 (6.2 g, yield 88.6%) as a white solid (M+1=258).

Example 4 Synthesis ofbenzyl-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-amine (9)(Compound 1-1, Table 1)

Step-1—Synthesis ofbenzyl-[5-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-amine(10).

Into a round bottom flask was added compound 6 (160.0 mg, 0.40 mmol),benzylamine (0.1 mL, 0.90 mmol), palladium acetate (17.0 mg, 0.076mmol), toluene (10.0 mL), potassium tert-butoxide (80.0 mg, 0.71 mmol)and 2-(di-t-butylphosphino)biphenyl (31.4 mg, 0.11 mmol) under anatmosphere of nitrogen. The reaction was stirred under reflux for 3hours. TLC and MS indicated no starting material. The reaction mixturewas poured into water, extracted with ethyl acetate. The organic layerwas washed with brine, dried over sodium sulfate, concentrated andpurified with biotage (methylene chloride/methanol 1:20) to give product10 (110 mg, yield=58.5%) as a white solid (M+1=471).

Step-2—Synthesis ofbenzyl-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-amine (9).

Into a round bottom flask was added compound 10 (400.0 mg, 0.85 mmol),tetrahydrofuran (20.0 mL) and tetra-n-butylammonium fluoride (240 mg,0.93 mmol). The reaction mixture was stirred at 20 Celsius for 30 min.TLC indicated no starting material. The reaction mixture was poured intowater, extracted with ethyl acetate. The organic layer was washed withbrine, dried over sodium sulfate, concentrated and purified with biotage(methylene chloride/methanol 1:10) to give product 9 (Table 1 Cmpd 1-1)(220 mg, Yield=82.4%) as a white solid (M+1=315).

Example 5 Synthesis of(6-Benzylamino-pyridin-3-yl)-(1H-pyrrolo[2,3-b]pyridin-3-yl)-methanone(11) (Compound 1-2, Table 1)

Into a pressure tube was added compound 7 (270.0 mg, 1.05 mmol),benzylamine (0.7 mL, 0.006 mol) and tetrahydrofuran (25.0 mL) under anatmosphere of nitrogen. The reaction mixture was heated to 185 Celsiusfor 60 hours. The reaction mixture was concentrated to remove most ofthe solvent and then the residue was poured into water and extractedwith ethyl acetate. The organic layer was dried over sodium sulfate,concentrated and purified with biotage (methylene chloride/methanol1:20) to give product 11 (Table 1 Cmpd 1-2) (30 mg, yield=8.7%) as awhite solid (M+1=329).

Additional compounds made by this route, replacing benzylamine with4-fluorobenzylamine, 3-fluorobenzylamine, 4-trifluoromethylbenzylamineand thiophen-2-yl methylamine to provide, respectively:

Example 6 Synthesis of[5-(1H-Pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(4-trifluoromethyl-benzyl)-amine(12) (Compound 1-3, Table 1)

Step-1—Synthesis of(1H-Pyrrolo[2,3-b]pyridin-3-yl)-[6-(4-trifluoromethyl-benzylamino)-pyridin-3-yl]-methanone(13).

Into a pressure flask was added compound 7 (3.5 g, 0.014 mol) and4-(trifluoromethyl)benzylamine (9.0 g, 0.051 mol) and tetrahydrofuran(30.0 mL, 0.37 mol) and palladium acetate (200.0 mg, 0.890 mmol) and2-(di-t-butylphosphino)biphenyl (200.0 mg, 0.67 mmol). The reactionmixture was stirred at 180 Celsius overnight, poured into water, andextracted with ethyl acetate. The organic layer was washed with brine,dried over sodium sulfate, concentrated. To the residue was added aceticacid (15.0 mL) and H₂O (5.0 mL). The reaction mixture was stirred at 100Celsius for 5 hours and concentrated to remove acetic acid. The residuewas then treated with aqueous Na₂HCO₃ and extracted with ethyl acetate.The organic layer was washed, dried, concentrated and purified to giveproduct 13 (1.0 g, yield=18.5%) as a light yellow solid (M+1=397).

Step-2—Synthesis of(1H-Pyrrolo[2,3-b]pyridin-3-yl)-[6-(4-trifluoromethyl-benzylamino)-pyridin-3-yl]-methanol(14).

Into a round bottom flask was added compound 13 (210.0 mg, 0.53 mmol)and sodium tetrahydroborate (80.0 mg, 2.11 mmol) and dissolved inN,N-dimethylformamide (5.0 mL) and ethanol (20.0 mL). The reaction wasstirred at room temperature overnight, poured into water, and theproduct was extracted with ethyl acetate. The organic layer was washedwith brine, dried over sodium sulfate, concentrated and purified withbiotage (methylene chloride/methanol 1:20) to give product 14 (63 mg,yield=30%) as a white solid (M+1=399)

Step-3—Synthesis of[5-(1H-Pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(4-trifluoromethyl-benzyl)-amine(12).

Into a round bottom flask was added compound 14 (200.0 mg, 0.50 mmol)and trifluoroacetic acid (5.0 mL, 0.065 mol) and triethylsilane (3.0 mL,0.019 mol). The reaction was stirred at room temperature for 30 min,poured into aqueous sodium bicarbonate, and the product was extractedwith ethyl acetate. The organic layer was washed with brine, dried oversodium sulfate, concentrated and purified to give pure product 12 (Table1 Cmpd 1-3) (120.0 mg, yield=62.8%) as a white solid (M+1=383).

Example 7 Synthesis of(4-methoxy-benzyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-amine(15) (Compound 1-4, Table 1)

Compound 15 (Table 1 Cmpd 1-4) was synthesized as shown in Scheme-6using compound 6, where X=Br, as a starting material and substituting4-methoxy benzyl amine for benzyl amine (M=344.4)

Example 8 Synthesis of(4-chloro-benzyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-amine(16) (Compound 1-5, Table 1)

Compound 16 (Table 1 Cmpd 1-5) was synthesized as shown in Scheme-6using compound 6, where X=Br, as a starting material and substituting4-chloro benzyl amine for benzyl amine (M=348.8)

Example 9 Synthesis of(4-fluoro-benzyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-amine(17) (Compound 1-6, Table 1)

Compound 17 (Table 1 Cmpd 1-6) was synthesized as shown in Scheme-6using compound 6, where X=Br, as a starting material and substituting4-fluoro benzyl amine for benzyl amine (M=332.4)

Example 10 Synthesis of(4-methyl-benzyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-amine(18) (Compound 1-7, Table 1)

Compound 18 (Table 1 Cmpd 1-7) was synthesized as shown in Scheme-6using compound 6, where X=Br, as a starting material and substituting4-methyl benzyl amine for benzyl amine (M=328.4)

Example 11 Synthesis of[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-thiophen-2-ylmethyl-amine(19) (Compound 1-8, Table 1)

Compound 19 (Table 1 Cmpd 1-8) was synthesized as shown in Scheme-6using compound 6, where X=Br, as a starting material and substituting2-thienyl-methyl amine for benzyl amine (M=330.4)

Example 12 cKit Kinase Domain and Construction of c-Kit Sequences

c-Kit cDNA sequence is available from NCBI, e.g., as GenBank accessionnumber NM_(—)000222 (SEQ ID NO:2). Using this sequence, c-Kit DNAsequences can be cloned from commercially available libraries (e.g.,cDNA libraries) or can be synthesized by conventional cloning methods.

Using conventional cloning methods, constructs encoding three c-Kitpolypeptides were prepared, and used to express c-Kit kinase domainpolypeptides. One such active c-Kit kinase domain sequence includedresidues P551-S948, with the deletion of residues Q694-T753,

Example 13 Expression and Purification of c-Kit Kinase Domain

Purified c-Kit kinase domain can be obtained using conventionalexpression and purification methods. Exemplary methods are described,for example, in Lipson et al., U.S. 20040002534 (U.S. application Ser.No. 10/600,868, filed Jun. 23, 2003), which is incorporated herein byreference in its entirety.

Example 14 Binding Assays

Binding assays can be performed in a variety of ways, including avariety of ways known in the art. For example, as indicated above,binding assays can be performed using fluorescence resonance energytransfer (FRET) format, or using an AlphaScreen

Alternatively, any method which can measure binding of a ligand to theATP-binding site can be used. For example, a fluorescent ligand can beused. When bound to c-Kit, the emitted fluorescence is polarized. Oncedisplaced by inhibitor binding, the polarization decreases.

Determination of IC₅₀ for compounds by competitive binding assays. (Notethat K₁ is the dissociation constant for inhibitor binding; K_(D) is thedissociation constant for substrate binding.) For this system, the IC₅₀,inhibitor binding constant and substrate binding constant can beinterrelated according to the following formula:

When using radiolabeled substrate

${K_{I} = \frac{I\; C_{50}}{1 + {\left\lbrack L^{*} \right\rbrack\text{/}K_{D}}}},$the IC₅₀˜K₁ when there is a small amount of labeled substrate.

Example 15 c-Kit Activity Assays

The effect of potential modulators of kinase activity of c-Kit and otherkinases can be measured in a variety of different assays known in theart, e.g., biochemical assays, cell-based assays, and in vivo testing(e.g., model system testing). Such in vitro and/or in vivo assays andtests can be used in the present invention.

In an exemplary biochemical assay, c-Kit kinase activity can bedetermined in the following assay format:

Exemplary Biochemical Assay

IC₅₀ values were determined with respect to inhibition of c-Kit kinaseactivity, where inhibition of phosphorylation of a peptide substrate ismeasured as a function of compound concentration. Compounds 1-3, 1-5,1-6, and 1-7 (Table 1) and 1-9 and 1-12 (Example 5) were dissolved inDMSO to a concentration of 20 mM. These were diluted 30 μl into 120 μlof DMSO (4 mM) and 1 μl was added to an assay plate. These were thenserially diluted 1:3 (50 μl to 100 μl DMSO) for a total of 8 points. Theplate was mixed vigorously for 10 seconds after each dilution. Thediluted samples were then distributed in 1 μl aliquots to an assayplate. 8 μl of substrate (Biotin-(E₄Y)₃, Open Source Biotech, Inc., 0.2mg/ml in DMSO), PE alpha PY20 (acceptor) and Streptavidin (donor) beads(PY20 AlphaScreening kit, Perkin Elmer Life Science Inc. catalog#676601M) were mixed in 5.5 ml of kinase buffer (50 mM HEPES, pH 7.2, 5mM MgCl₂, 5 mM MnCl₂, 0.1% NP-40, 50 μg/ml BSA). C-Kit kinase domain(starting amino acid M551, ending amino acid K949) was prepared byexpression of plasmid P1332 (pET-N6 BI-PTP, N-terminal non-cleavable Histag and bicistronic PTP) in E. coli, added to the solution and mixedwell. This was distributed into a polypropylene plate at 50 μl per well,then transferred 10 μl to each well of the assay plate, shaking theplate for 20 seconds to mix (final c-Kit of 50 ng/well). ATP (100 mMstock) was diluted 1 μl into 5 ml of kinase buffer and the solutionmixed well, 50 μl per well was transferred to a polypropylene plate,then 10 μl per well transferred to the assay plate (final ATP 10 μM).The plate was shaken for 30 seconds, then incubated for 30 minutes at30° C. Added 5 μl per well of stop buffer (50 mM EDTA in kinase buffer)and incubated for 30 minutes at room temperature, then read the signalper well on AlphaQuest reader. Phosphorylated substrate results inbinding of the PY20 antibody and association of the donor and acceptorbeads such that signal correlates with kinase activity. The signal vs.compound concentration was used to determine the IC₅₀. Compounds 1-3,1-5, 1-6 and 1-7 (Table 1) were similarly assayed, using in a finalreaction volume of 25 μl: c-Kit (h) (5-10 mU) in 8 mM MOPS pH 7.0, 0.2mM EDTA, 10 mM MnCl₂, 0.1 mg/ml poly (Glu, Tyr) 4:1, mM MgAcetate andγ-³³P-ATP (approximately 500 cpm/pmol), with appropriate concentrationsof compound. Incubated for 40 minutes at room temperature and stopped byaddition of 5 μl of 3% phosphoric acid. Spotted 10 μl of each sampleonto Filtermat A and washed 3× with 75 mM phosphoric acid, once withmethanol, dried and measured on scintillation counter (performed atUpstate USA, Charlottesville, Va.). All compounds had IC₅₀ of less than1 μM as measured by at least one of these assays.

Additional Biochemical and Cell-Based Assays

In general, any protein kinase assay can be adapted for use with c-Kit.For example, assays (e.g., biochemical and cell-based assays) asdescribed in Lipson et al., U.S. Patent Publ. 20040002534 (incorporatedherein by reference in its entirety) can be used in the presentinvention.

As one example, M-07e cell line (DSMZ catalog #ACC 104) proliferation isstimulated by SCF (Stem Cell Factor), which binds and activates c-Kittyrosine kinase receptor. Inhibitors of c-Kit kinase reduce or eliminatethe SCF mediated kinase activation, resulting in reduced cellproliferation of SCF stimulated cells. This inhibition is measured bythe effect of compound concentration on cell growth to assess IC₅₀values. M-07e cells were seeded at 5×10⁴ cells per well of a 96 wellcell culture plate in 50 μl of cell culture medium of Iscove's Medium 1×(MOD, CellGro Mediatech catalog #15-016-CV) supplemented with 10% FBS(HyClone catalog #SH30071.03). Compounds 1-3 and 1-5 (Table 1) weredissolved in DMSO at a concentration of 0.1 mM and were serially diluted1:3 for a total of eight points and added to the cells to finalconcentrations of 1, 0.33, 0.11, 0.037, 0.012, 0.0041, 0.0014 and0.00046 μM in 100 μl cell culture medium (final concentration 0.8%DMSO). Cells were also treated with staurosporine as a positive control.Cells were stimulated by adding 20 μl of 600 ng/ml SCF to a finalconcentration of 100 ng/ml (Biosource International SCF kit ligandcatalog #PHC2115) in cell culture medium. The cells were incubated at37° C., 5% CO₂ for three days. CellTiter-Glo Buffer (Promega CellViability Assay catalog #G7573) and substrate were equilibrated to roomtemperature, and enzyme/substrate Recombinant Firefly Luciferase/BeetleLuciferin was reconstituted. The cell plates were equilibrated to roomtemperature for 30 minutes, then lysed by addition of an equivalentvolume of the Celltiter-Glo Reagent. The plate was mixed for 2 minuteson a plate shaker to lyse the cells, then incubated for 10 minutes atroom temperature. The plates were read on a Victor Wallac II usingLuminescence protocol modified to read 0.1 s per well. The luminescencereading assesses the ATP content, which correlates directly with cellnumber such that the reading as a function of compound concentration isused to determine the IC₅₀ value. Both compounds had IC₅₀ of less than 1μM.

This cell based assay was also used to assess phosphorylation. Sampleswere prepared as described for the growth inhibition assay only M-07ecells were seeded at 2×10⁵ cells per well in a 96 well filter plate.Cells were incubated for 1 hour at 37° C. with the compounds asdescribed above, and then stimulated by adding SCF to a finalconcentration of 50 ng/ml and incubated for 10 minutes at 37° C. Theculture medium was removed by centrifugation and the cells were lysed byaddition of 30 μl lysis buffer (25 mM Tris HCl pH 7.5, 150 mM NaCl, 5 mMEDTA, 1% Triton X100, 5 mM NaF, 1 mM NaVanadate, 10 mMBeta-glycerophosphate, no EDTA (Boehringer-Roche catalog #1873580) andplaced on ice for 30 minutes. A 15 μl aliquot of the lysate was takenand assayed according to Biosource Immunoassay Kit: Human c-Kit [pY823](Catalog #KHO0401) by diluting the aliquot with 85 μl dilution buffer inthe assay plate, incubating for 2 hours at room temperature and washingthe plate 4 times with wash buffer. Detection antibody (100 μl) wasadded to the plate and samples incubated for 1 hour at room temperature,then washed 4 times with wash buffer. HRP anti-rabbit antibody (100 μl)was added and samples incubated for 30 minutes at room temperature, thenwashed 4 times with wash buffer. Stabilized chromogen (100 μl) was addedand samples incubated for 15-25 minutes at room temperature, then washed4 times with wash buffer. Stop solution (100 μl) was added and thesamples read on a Wallac Victor reader at 450 nm. The absorbance wasplotted against the compound concentration and the IC₅₀ concentrationwas determined. Both compounds had IC₅₀ of less than 1 μM.

In Vivo Model System Testing

For in vivo testing, a suitable animal model system can be selected foruse. For example, for multiple scerosis, the rodent experimentalallergic encephalomyelitis (EAE) is commently used. This system iswell-known, and is described, for example, in Steinman, 1996, Cell85:299-302 and Secor et al., 2000, J Exp. Med. 5:813-821, which areincorporated herein by reference in their entireties.

Similarly, other model systems can be selected and used in the presentinvention.

Example 16 Site-Directed Mutagenesis of c-Kit and Other Kinases

Mutagenesis of c-Kit and other kinases (as well as other sequences ofinterest) can be carried out according to the following procedure asdescribed in Molecular Biology: Current Innovations and Future Trends.Eds. A. M. Griffin and H. G. Griffin. (1995) ISBN 1-898486-01-8, HorizonScientific Press, PO Box 1, Wymondham, Norfolk, U.K., among others.

In vitro site-directed mutagenesis is an invaluable technique forstudying protein structure-function relationships, gene expression andvector modification. Several methods have appeared in the literature,but many of these methods require single-stranded DNA as the template.The reason for this, historically, has been the need for separating thecomplementary strands to prevent reannealing. Use of PCR insite-directed mutagenesis accomplishes strand separation by using adenaturing step to separate the complementing strands and allowingefficient polymerization of the PCR primers. PCR site-directed methodsthus allow site-specific mutations to be incorporated in virtually anydouble-stranded plasmid; eliminating the need for M13-based vectors orsingle-stranded rescue.

It is often desirable to reduce the number of cycles during PCR whenperforming PCR-based site-directed mutagenesis to prevent clonalexpansion of any (undesired) second-site mutations. Limited cyclingwhich would result in reduced product yield, is offset by increasing thestarting template concentration. A selection is used to reduce thenumber of parental molecules coming through the reaction. Also, in orderto use a single PCR primer set, it is desirable to optimize the long PCRmethod. Further, because of the extendase activity of some thermostablepolymerases it is often necessary to incorporate an end-polishing stepinto the procedure prior to end-to-end ligation of the PCR-generatedproduct containing the incorporated mutations in one or both PCRprimers.

The following protocol provides a facile method for site-directedmutagenesis and accomplishes the above desired features by theincorporation of the following steps: (i) increasing templateconcentration approximately 1000-fold over conventional PCR conditions;(ii) reducing the number of cycles from 25-30 to 5-10; (iii) adding therestriction endonuclease DpnI (recognition target sequence: 5-Gm6ATC-3,where the A residue is methylated) to select against parental DNA (note:DNA isolated from almost all common strains of E. coli is Dam-methylatedat the sequence 5-GATC-3); (iv) using Taq Extender in the PCR mix forincreased reliability for PCR to 10 kb; (v) using Pfu DNA polymerase topolish the ends of the PCR product, and (vi) efficient intramolecularligation in the presence of T4 DNA ligase.

Plasmid template DNA (approximately 0.5 pmole) is added to a PCRcocktail containing, in 25 ul of 1× mutagenesis buffer: (20 mM Tris HCl,pH 7.5; 8 mM MgCl₂; 40 ug/ml BSA); 12-20 pmole of each primer (one ofwhich must contain a 5-prime phosphate), 250 uM each dNTP, 2.5 U Taq DNApolymerase, 2.5 U of Taq Extender (Stratagene).

The PCR cycling parameters are 1 cycle of: 4 min at 94 C, 2 min at 50 Cand 2 min at 72° C.; followed by 5-10 cycles of 1 min at 94° C., 2 minat 54 C and 1 min at 72° C. (step 1).

The parental template DNA and the linear, mutagenesis-primerincorporating newly synthesized DNA are treated with DpnI (10 U) and PfuDNA polymerase (2.5 U). This results in the DpnI digestion of the invivo methylated parental template and hybrid DNA and the removal, by PfuDNA polymerase, of the Taq DNA polymerase-extended base(s) on the linearPCR product.

The reaction is incubated at 37° C. for 30 ml and then transferred to72° C. for an additional 30 min (step 2).

Mutagenesis buffer (1×, 115 ul, containing 0.5 mM ATP) is added to theDpnI-digested, Pfu DNA polymerase-polished PCR products.

The solution is mixed and 10 μl is removed to a new microfuge tube andT4 DNA ligase (2-4 U) added.

The ligation is incubated for greater than 60 min at 37° C. (step 3).

The treated solution is transformed into competent E. coli (step 4).

In addition to the PCR-based site-directed mutagenesis described above,other methods are available. Examples include those described in Kunkel(1985) Proc. Natl. Acad. Sci. 82:488-492; Eckstein et al. (1985) Nucl.Acids Res. 13:8764-8785; and using the GeneEditor™ Site-DirectedMutagenesis System from Promega.

All patents and other references cited in the specification areindicative of the level of skill of those skilled in the art to whichthe invention pertains, and are incorporated by reference in theirentireties, including any tables and figures, to the same extent as ifeach reference had been incorporated by reference in its entiretyindividually.

One skilled in the art would readily appreciate that the presentinvention is well adapted to obtain the ends and advantages mentioned,as well as those inherent therein. The methods, variances, andcompositions described herein as presently representative of preferredembodiments are exemplary and are not intended as limitations on thescope of the invention. Changes therein and other uses will occur tothose skilled in the art, which are encompassed within the spirit of theinvention, are defined by the scope of the claims.

It will be readily apparent to one skilled in the art that varyingsubstitutions and modifications may be made to the invention disclosedherein without departing from the scope and spirit of the invention. Forexample, variations can be made to provide additional compounds ofFormula I and/or various methods of administration can be used. Thus,such additional embodiments are within the scope of the presentinvention and the following claims.

The invention illustratively described herein suitably may be practicedin the absence of any element or elements, limitation or limitationswhich is not specifically disclosed herein. The terms and expressionswhich have been employed are used as terms of description and not oflimitation, and there is no intention that in the use of such terms andexpressions of excluding any equivalents of the features shown anddescribed or portions thereof, but it is recognized that variousmodifications are possible within the scope of the invention claimed.Thus, it should be understood that although the present invention hasbeen specifically disclosed by preferred embodiments and optionalfeatures, modification and variation of the concepts herein disclosedmay be resorted to by those skilled in the art, and that suchmodifications and variations are considered to be within the scope ofthis invention as defined by the appended claims.

In addition, where features or aspects of the invention are described interms of Markush groups or other grouping of alternatives, those skilledin the art will recognize that the invention is also thereby describedin terms of any individual member or subgroup of members of the Markushgroup or other group.

Also, unless indicated to the contrary, where various numerical valuesare provided for embodiments, additional embodiments are described bytaking any 2 different values as the endpoints of a range. Such rangesare also within the scope of the described invention.

Thus, additional embodiments are within the scope of the invention andwithin the following claims.

1. A method for treating a subject suffering from or at risk of a c-Kitmediated disease or condition selected from the group consisting ofmultiple sclerosis, rheumatoid arthritis, thyroid cancer, leukemia, andgastrointestinal tract cancer, said method comprising: administering tosaid subject an effective amount of a compound of

or a salt or isomer thereof, wherein: R¹ and R⁵ are independentlyselected from the group consisting of hydrogen, halo, hydroxy,substituted oxy, thiol, substituted thiol, optionally substituted loweralkyl, optionally substituted lower alkenyl, optionally substitutedlower alkynyl, optionally substituted cycloalkyl, optionally substitutedcycloalkylalkyl, optionally substituted heterocyclyl, optionallysubstituted heterocyclylalkyl, optionally substituted aryl, optionallysubstituted aralkyl, optionally substituted heteroaryl, optionallysubstituted heteroaralkyl, —C(X)NR¹⁶R¹⁷, —C(X)R²⁰, and —NR²²R²³; R³ andR⁴ are independently selected from the group consisting of hydrogen,halo, hydroxy, substituted oxy, thiol, substituted thiol, optionallysubstituted lower alkyl, optionally substituted lower alkenyl,optionally substituted lower alkynyl, optionally substituted cycloalkyl,optionally substituted cycloalkylalkyl, optionally substitutedheterocyclyl, optionally substituted heterocyclylalkyl, optionallysubstituted aryl, optionally substituted aralkyl, optionally substitutedheteroaryl, optionally substituted heteroaralkyl, —C(X)R²⁰,—C(X)NR¹⁶R¹⁷, —S(O)₂NR¹⁶R¹⁷, —NR²²R²³, and —S(O)_(n)R²¹; R² is—X¹—X²—X³—X⁴, wherein: X¹ is selected from the group consisting of loweralkylene, substituted lower alkylene, —C(O)—, —CH₂C(O)—, —C(O)CH₂—,—C(S)—, —CH₂C(S)—, —C(S)CH₂—, —O—, —S—, —S(O₂)—, and —NR^(a)—, wherein: R^(a) is selected from the group consisting of hydrogen, lower alkyland lower alkyl substituted with fluoro, hydroxyl, alkoxy, thiol,thioalkoxy, or amino, provided, however, that hydroxyl, alkoxy, thiol,thioalkyoxy or amino are not substituted at the carbon bound to thenitrogen of —NR^(a)—; X² is pyridinyl; X³ is selected from the groupconsisting of

wherein:  R^(b) at each occurrence is independently selected from thegroup consisting of hydrogen, lower alkyl and lower alkyl substitutedwith fluoro, hydroxyl, alkoxy, thiol, thioalkoxy, or amino, provided,however, that hydroxyl, alkoxy, thiol, thioalkyoxy or amino are notsubstituted at the carbon bound to the nitrogen of NR^(b); and  R^(c) isselected from the group consisting of alkylene and substituted alkylene;and X⁴ is

wherein  C² is selected from the group consisting of aryl andheteroaryl;  R^(d) is selected from the group consisting of halogen,lower alkyl, substituted lower alkyl, optionally substituted loweralkoxy, optionally substituted alkylthio, optionally substitutedalkenyl, optionally substituted alkynyl, optionally substituted amine,optionally substituted amido, carboxyl, hydroxyl, optionally substitutedaryl, aryloxy, optionally substituted heterocycle, optionallysubstituted heteroaryl, nitro, cyano, thiol, and sulfonylamino; and  mis in the range 0-2; R¹⁶ and R¹⁷ are independently selected from thegroup consisting of hydrogen, optionally substituted lower alkyl,optionally substituted lower alkenyl, provided, however, that nitrogenis not attached to the alpha carbon of the alkene bond; optionallysubstituted lower alkynyl, provided, however, that nitrogen is notattached to the alpha carbon of the alkyne bond; optionally substitutedcycloalkyl, optionally substituted cycloalkylalkyl, optionallysubstituted heterocyclyl, optionally substituted heterocyclylalkyl,optionally substituted aryl, optionally substituted aralkyl, optionallysubstituted heteroaryl, and optionally substituted heteroaralkyl; or R¹⁶and R¹⁷ together with the nitrogen form an optionally substituted 5-7membered heterocyclic or heteroaryl ring; R²⁰ is selected from the groupconsisting of hydroxyl, substituted oxy, optionally substituted amine,optionally substituted lower alkyl, optionally substituted loweralkenyl, provided, however, that —C(X)— is not attached to the alphacarbon of the alkene bond, optionally substituted lower alkynyl,provided, however, that —C(X)— is not attached to the alpha carbon ofthe alkyne bond, optionally substituted cycloalkyl, optionallysubstituted cycloalkylalkyl, optionally substituted heterocyclyl,optionally substituted heterocyclylalkyl, optionally substituted aryl,optionally substituted aralkyl, optionally substituted heteroaryl, andoptionally substituted heteroaralkyl; R²¹ is selected from the groupconsisting of hydrogen provided n=0, optionally substituted lower alkyl,optionally substituted amine, optionally substituted lower alkenyl,provided, however, that —S(O)_(n)— is not attached to the alpha carbonof the alkene bond, optionally substituted lower alkynyl, provided,however, that —S(O)_(n)— is not attached to the alpha carbon of thealkyne bond, optionally substituted cycloalkyl, optionally substitutedcycloalkylalkyl, optionally substituted heterocyclyl, optionallysubstituted heterocyclylalkyl, optionally substituted aryl, optionallysubstituted aralkyl, optionally substituted heteroaryl, and optionallysubstituted heteroaralkyl; R²² and R²³ are independently selected fromthe group consisting of hydrogen, optionally substituted lower alkyl,optionally substituted lower alkenyl, provided, however, that nitrogenis not attached to the alpha carbon of the alkene bond, optionallysubstituted lower alkynyl, provided, however, that nitrogen is notattached to the alpha carbon of the alkyne bond, optionally substitutedcycloalkyl, optionally substituted cycloalkylalkyl, optionallysubstituted heterocyclyl, optionally substituted heterocyclylalkyl,optionally substituted aryl, optionally substituted aralkyl, optionallysubstituted heteroaryl, optionally substituted heteroaralkyl, —C(X)R²⁰,—C(X)NR¹⁶R¹⁷, and —S(O)₂R²¹; or R²² and R²³ together with the nitrogenform an optionally substituted 5-7 membered heterocyclic or heteroarylring; X is selected from the group consisting of O and S; and n is 0, 1,or
 2. 2. The method of claim 1 wherein said c-Kit mediated disease orcondition is associated with improperly regulated kinase signaltransduction.
 3. The method of claim 2 wherein said improperly regulatedkinase signal transduction is of mast cells.
 4. The method of claim 1wherein said c-Kit mediated disease or condition is rheumatoidarthritis.
 5. The method of claim 1 wherein said c-Kit mediated diseaseor condition is leukemia.
 6. The method of claim 1 wherein said c-Kitmediated disease or condition is thyroid cancer.
 7. The method of claim1 wherein said mediated disease or condition is cancer of thegastrointestinal tract.
 8. The method of claim 1 wherein said c-Kitmediated disease or condition is multiple sclerosis.
 9. A method fortreating a subject suffering from or at risk of a c-Kit mediated diseaseor condition selected from the group consisting of multiple sclerosis,rheumatoid arthritis, thyroid cancer, leukemia, and gastrointestinaltract cancer, said method comprising: administering to said subject aneffective amount of a compound having a structure:

or a salt or isomer thereof, wherein: R² is X¹—X²—X³—X⁴; X¹ is selectedfrom the group consisting of lower alkylene, substituted lower alkylene,—C(O)—, —CH₂—C(O)—, —C(O)CH₂—, —C(S)—, —CH₂—C(S)—, —C(S)CH₂—, —O—, —S—,—S(O₂)— and —NR^(a)—, wherein R^(a) is selected from the groupconsisting of hydrogen, lower alkyl and lower alkyl substituted withfluoro, hydroxyl, alkoxy, thiol, thioalkoxy, or amino, provided,however, that hydroxyl, alkoxy, thiol, thioalkyoxy or amino are notsubstituted at the carbon bound to the nitrogen of —NR^(a)—; X² ispyridinyl; X³ is selected from the group consisting of

wherein R^(b) at each occurrence is independently selected from thegroup consisting of hydrogen, lower alkyl and lower alkyl substitutedwith fluoro, hydroxyl, alkoxy, thiol, thioalkoxy, or amino, provided,however, that hydroxyl, alkoxy, thiol, thioalkyoxy or amino are notsubstituted at the carbon bound to the nitrogen of NR^(b); and R^(c) isselected from the group consisting of alkylene and substituted alkylene;and X⁴ is

wherein C² is selected from the group consisting of aryl and heteroaryl;R^(d) is selected from the group consisting of halogen, lower alkyl,substituted lower alkyl, optionally substituted lower alkoxy, optionallysubstituted alkylthio, optionally substituted alkenyl, optionallysubstituted alkyknyl, optionally substituted amine, optionallysubstituted amido, carboxyl, hydroxyl, optionally substituted aryl,aryloxy, optionally substituted heterocycle, optionally substitutedheteroaryl, nitro, cyano, thiol, and sulfonylamino; and m is in therange 0-2.
 10. The method of claim 9 wherein said c-Kit mediated diseaseor condition is associated with improperly regulated kinase signaltransduction.
 11. The method of claim 10 wherein said improperlyregulated kinase signal transduction is of mast cells.
 12. The method ofclaim 9 wherein said c-Kit mediated disease or condition is rheumatoidarthritis.
 13. The method of claim 9 wherein said c-Kit mediated diseaseor condition is leukemia.
 14. The method of claim 9 wherein said c-Kitmediated disease or condition is thyroid cancer.
 15. The method of claim9 wherein said c-Kit mediated disease or condition is cancer of thegastrointestinal tract.
 16. The method of claim 9 wherein said c-Kitmediated disease or condition is multiple sclerosis.
 17. A method fortreating a subject suffering from or at risk of a c-Kit mediated diseaseor condition, said method comprising: administering to said subject aneffective amount of a compound selected from the group consisting of:benzyl-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-amine;(6-Benzylamino-pyridin-3-yl)-(1H-pyrrolo[2,3-b]pyridin-3-yl)-methanone;[5-(1H-Pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-(4-trifluoromethyl-benzyl)-amine;(4-methoxy-benzyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-amine;(4-chloro-benzyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-amine;(4-fluoro-benzyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-amine;(4-methyl-benzyl)-[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-amine;and[5-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-pyridin-2-yl]-thiophen-2-ylmethyl-amine,wherein the disease or condition is selected from the group consistingof multiple sclerosis, rheumatoid arthritis, thyroid cancer, leukemia,and gastrointestinal tract cancer.
 18. The method of claim 17, whereinsaid c-Kit mediated disease or condition is rheumatoid arthritis. 19.The method of claim 17, wherein said c-Kit mediated disease or conditionis a thyroid cancer.
 20. The method of claim 17, wherein said c-Kitmediated disease or condition is a cancer of the gastrointestinal tract.21. The method of claim 17, wherein said c-Kit mediated disease orcondition is multiple sclerosis.
 22. The method of claim 17, whereinsaid c-Kit mediated disease or condition is leukemia.